TY  - CONF
AU  - Opsenica, Igor
AU  - Koračak, Ljiljana
AU  - Lupšić, Ema
AU  - Jovanović, Mirna
AU  - Novaković, Miroslav
AU  - Pešić, Milica
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6382
AB  - Derivatization of artemisinin, a natural sesquiterpene lactone, and its synthetic analog artesunate, is of significant interest in medicinal chemistry due to their versatile biological activity, including antimalarial and anticancer. The importance of the pyrimidine scaffold in medicinal chemistry is evidenced by its presence in many natural products and approved drugs, as well as in numerous biologically active compounds.
In this study, we report the synthesis of several novel hybrid molecules comprising two pharmacophores
(artesunic acid and pyrimidine scaffold) and their activity against sensitive and multidrug‐resistant (MDR)
human non‐small cell lung carcinoma (NSCLC) cells. The synthesis of novel artemisinin-pyrimidine hybrid
molecules was accomplished via amide bond formation between artesunic acid and pyrimidine derivatives. A lead compound was identified through structure activity relationship (SAR) studies. Several hybrids were capable of evading the MDR phenotype, increasing the sensitivity of MDR NSCLC cells toward doxorubicin and displayed inhibitory activity against P-glycoprotein.
PB  - Cambridge: Royal Society of Chemistry
C3  - Book of abstracts: 22nd European Symposium on Organic Chemistry Ghent: ESOC23GHENT; 2023 Jul 9-13; Ghent, Belgium
T1  - Synthesis of Novel Artemisinin Derivatives With Potent Anticancer Activities Against Multidrug-resistant Cancer Cells
SP  - 213
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6382
ER  - 

@conference{
author = "Opsenica, Igor and Koračak, Ljiljana and Lupšić, Ema and Jovanović, Mirna and Novaković, Miroslav and Pešić, Milica",
year = "2023",
abstract = "Derivatization of artemisinin, a natural sesquiterpene lactone, and its synthetic analog artesunate, is of significant interest in medicinal chemistry due to their versatile biological activity, including antimalarial and anticancer. The importance of the pyrimidine scaffold in medicinal chemistry is evidenced by its presence in many natural products and approved drugs, as well as in numerous biologically active compounds.
In this study, we report the synthesis of several novel hybrid molecules comprising two pharmacophores
(artesunic acid and pyrimidine scaffold) and their activity against sensitive and multidrug‐resistant (MDR)
human non‐small cell lung carcinoma (NSCLC) cells. The synthesis of novel artemisinin-pyrimidine hybrid
molecules was accomplished via amide bond formation between artesunic acid and pyrimidine derivatives. A lead compound was identified through structure activity relationship (SAR) studies. Several hybrids were capable of evading the MDR phenotype, increasing the sensitivity of MDR NSCLC cells toward doxorubicin and displayed inhibitory activity against P-glycoprotein.",
publisher = "Cambridge: Royal Society of Chemistry",
journal = "Book of abstracts: 22nd European Symposium on Organic Chemistry Ghent: ESOC23GHENT; 2023 Jul 9-13; Ghent, Belgium",
title = "Synthesis of Novel Artemisinin Derivatives With Potent Anticancer Activities Against Multidrug-resistant Cancer Cells",
pages = "213",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6382"
}

Opsenica, I., Koračak, L., Lupšić, E., Jovanović, M., Novaković, M.,& Pešić, M.. (2023). Synthesis of Novel Artemisinin Derivatives With Potent Anticancer Activities Against Multidrug-resistant Cancer Cells. in Book of abstracts: 22nd European Symposium on Organic Chemistry Ghent: ESOC23GHENT; 2023 Jul 9-13; Ghent, Belgium
Cambridge: Royal Society of Chemistry., 213.
https://hdl.handle.net/21.15107/rcub_ibiss_6382

Opsenica I, Koračak L, Lupšić E, Jovanović M, Novaković M, Pešić M. Synthesis of Novel Artemisinin Derivatives With Potent Anticancer Activities Against Multidrug-resistant Cancer Cells. in Book of abstracts: 22nd European Symposium on Organic Chemistry Ghent: ESOC23GHENT; 2023 Jul 9-13; Ghent, Belgium. 2023;:213.
https://hdl.handle.net/21.15107/rcub_ibiss_6382 .

Opsenica, Igor, Koračak, Ljiljana, Lupšić, Ema, Jovanović, Mirna, Novaković, Miroslav, Pešić, Milica, "Synthesis of Novel Artemisinin Derivatives With Potent Anticancer Activities Against Multidrug-resistant Cancer Cells" in Book of abstracts: 22nd European Symposium on Organic Chemistry Ghent: ESOC23GHENT; 2023 Jul 9-13; Ghent, Belgium (2023):213,
https://hdl.handle.net/21.15107/rcub_ibiss_6382 .

TY  - CONF
AU  - Koračak, Ljiljana K.
AU  - Lupšić, Ema
AU  - Jovanović, Mirna
AU  - Novaković, Miroslav
AU  - Pešić, Milica
AU  - Opsenica, Igor M.
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6383
AB  - Značaj artemizinina i njegovih derivata se ogleda u biološkoj aktivnosti jer osim što su
našli primjenu kao efikasni lijekovi za liječenje malarije, pokazuju i antitumorsku
aktivnost. Pirimidinsko jezgro je važno zbog prisustva ovog strukturnog motiva u
prirodnim proizvodima, u odobrenim lijekovima, ali i u biološki aktivnim molekulima. U
okviru ovog istraživanja prijavljena je sinteza novih hibridnih molekula dobijenih
povezivanjem dvije farmakofore, kao i njihova antitumorska aktivnost na rezistentnim i
osjetljivim ćelijama nesitnoćelijskog karcinoma pluća.
AB  - In addition to being used for the effective treatment of malaria, artemisinin and derivatives also exhibit anticancer activity. The importance of the pyrimidine scaffold is evidenced by its presence in natural products and approved drugs, as well as in biologically active compounds. In this study, we report the synthesis of novel hybrid molecules comprising two pharmacophores and their activity against sensitive and multidrug‐resistant human non‐small cell lung carcinoma cells.
PB  - Belgrade: Serbian Chemical Society
C3  - Book of Abstracts and Proceedings: 59th meeting of the Serbian Chemical Society; 2023 Jun 1-2; Novi Sad, Serbia
T1  - Sinteza novih derivata artemizinina sa antitumorskom aktivnošću na rezistentne ćelije raka
T1  - Synthesis of novel artemisinin derivatives with anticancer activity against multidrug-resistant cancer cells
SP  - 70
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6383
ER  - 

@conference{
author = "Koračak, Ljiljana K. and Lupšić, Ema and Jovanović, Mirna and Novaković, Miroslav and Pešić, Milica and Opsenica, Igor M.",
year = "2023",
abstract = "Značaj artemizinina i njegovih derivata se ogleda u biološkoj aktivnosti jer osim što su
našli primjenu kao efikasni lijekovi za liječenje malarije, pokazuju i antitumorsku
aktivnost. Pirimidinsko jezgro je važno zbog prisustva ovog strukturnog motiva u
prirodnim proizvodima, u odobrenim lijekovima, ali i u biološki aktivnim molekulima. U
okviru ovog istraživanja prijavljena je sinteza novih hibridnih molekula dobijenih
povezivanjem dvije farmakofore, kao i njihova antitumorska aktivnost na rezistentnim i
osjetljivim ćelijama nesitnoćelijskog karcinoma pluća., In addition to being used for the effective treatment of malaria, artemisinin and derivatives also exhibit anticancer activity. The importance of the pyrimidine scaffold is evidenced by its presence in natural products and approved drugs, as well as in biologically active compounds. In this study, we report the synthesis of novel hybrid molecules comprising two pharmacophores and their activity against sensitive and multidrug‐resistant human non‐small cell lung carcinoma cells.",
publisher = "Belgrade: Serbian Chemical Society",
journal = "Book of Abstracts and Proceedings: 59th meeting of the Serbian Chemical Society; 2023 Jun 1-2; Novi Sad, Serbia",
title = "Sinteza novih derivata artemizinina sa antitumorskom aktivnošću na rezistentne ćelije raka, Synthesis of novel artemisinin derivatives with anticancer activity against multidrug-resistant cancer cells",
pages = "70",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6383"
}

Koračak, L. K., Lupšić, E., Jovanović, M., Novaković, M., Pešić, M.,& Opsenica, I. M.. (2023). Sinteza novih derivata artemizinina sa antitumorskom aktivnošću na rezistentne ćelije raka. in Book of Abstracts and Proceedings: 59th meeting of the Serbian Chemical Society; 2023 Jun 1-2; Novi Sad, Serbia
Belgrade: Serbian Chemical Society., 70.
https://hdl.handle.net/21.15107/rcub_ibiss_6383

Koračak LK, Lupšić E, Jovanović M, Novaković M, Pešić M, Opsenica IM. Sinteza novih derivata artemizinina sa antitumorskom aktivnošću na rezistentne ćelije raka. in Book of Abstracts and Proceedings: 59th meeting of the Serbian Chemical Society; 2023 Jun 1-2; Novi Sad, Serbia. 2023;:70.
https://hdl.handle.net/21.15107/rcub_ibiss_6383 .

Koračak, Ljiljana K., Lupšić, Ema, Jovanović, Mirna, Novaković, Miroslav, Pešić, Milica, Opsenica, Igor M., "Sinteza novih derivata artemizinina sa antitumorskom aktivnošću na rezistentne ćelije raka" in Book of Abstracts and Proceedings: 59th meeting of the Serbian Chemical Society; 2023 Jun 1-2; Novi Sad, Serbia (2023):70,
https://hdl.handle.net/21.15107/rcub_ibiss_6383 .

TY  - CONF
AU  - Lupšić, Ema
AU  - Stepanović, Ana
AU  - Stojković, Pavle
AU  - Terzić-Jpvanović, Nataša
AU  - Novaković, Miroslav
AU  - Nedialkov, Paraskev
AU  - Trendafilova, Antoaneta
AU  - Opsenica, Igor M.
AU  - Pešić, Milica
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5928
AB  - Background: Glioblastoma is a highly aggressive and resistant brain tumor. P-glycoprotein
(P-gp) constitutes the blood-brain barrier and is expressed on the cell membrane of multidrugresistant (MDR) glioblastoma cells. Our objective was to investigate the anti-glioblastoma
effects of sclareol (SCL), a natural diterpene alcohol, and its two derivatives (11c and 12l).
Methods: Our cellular model included human glioblastoma U87 cell line without P-gp
expression, its MDR counterpart U87-TxR with P-gp expression, and normal lung fibroblasts
MRC-5. Cytotoxic effects were examined by MTT. P-gp function, cell cycle disturbance,
time-dependent cell death induction, the level of reactive oxygen and nitrogen species, and
changes in the mitochondrial membrane potential were studied by flow cytometry. Results:
SCL and its derivatives evaded the MDR in glioblastoma cells, showing lower IC50 values in
U87-TxR than in U87, referred to as collateral sensitivity. Both derivatives were more potent
than SCL, while 12l was active in the nanomolar range. 11c and 12l displayed greater
selectivity towards glioblastoma cells compared to SCL. All compounds significantly
disturbed the cell cycle and induced cell death: SCL - late apoptosis and necrosis, 11c - only
early apoptosis, and 12l - early and late apoptosis. SCL and its derivatives acted as
antioxidants, while 11c and 12l decreased mitochondrial membrane potential. Conclusion:
SCL derivatives were more potent than SCL. The observed collateral sensitivity in
glioblastoma cells can be explained by oxidative stress modulation because although resistant
due to P-gp expression, U87-TxR cells are more susceptible to changes in oxidative status
than U87 cells.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Evading multidrug resistance in glioblastoma with natural compound sclareol and its novel derivatives
SP  - 72
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5928
ER  - 

@conference{
author = "Lupšić, Ema and Stepanović, Ana and Stojković, Pavle and Terzić-Jpvanović, Nataša and Novaković, Miroslav and Nedialkov, Paraskev and Trendafilova, Antoaneta and Opsenica, Igor M. and Pešić, Milica",
year = "2023",
abstract = "Background: Glioblastoma is a highly aggressive and resistant brain tumor. P-glycoprotein
(P-gp) constitutes the blood-brain barrier and is expressed on the cell membrane of multidrugresistant (MDR) glioblastoma cells. Our objective was to investigate the anti-glioblastoma
effects of sclareol (SCL), a natural diterpene alcohol, and its two derivatives (11c and 12l).
Methods: Our cellular model included human glioblastoma U87 cell line without P-gp
expression, its MDR counterpart U87-TxR with P-gp expression, and normal lung fibroblasts
MRC-5. Cytotoxic effects were examined by MTT. P-gp function, cell cycle disturbance,
time-dependent cell death induction, the level of reactive oxygen and nitrogen species, and
changes in the mitochondrial membrane potential were studied by flow cytometry. Results:
SCL and its derivatives evaded the MDR in glioblastoma cells, showing lower IC50 values in
U87-TxR than in U87, referred to as collateral sensitivity. Both derivatives were more potent
than SCL, while 12l was active in the nanomolar range. 11c and 12l displayed greater
selectivity towards glioblastoma cells compared to SCL. All compounds significantly
disturbed the cell cycle and induced cell death: SCL - late apoptosis and necrosis, 11c - only
early apoptosis, and 12l - early and late apoptosis. SCL and its derivatives acted as
antioxidants, while 11c and 12l decreased mitochondrial membrane potential. Conclusion:
SCL derivatives were more potent than SCL. The observed collateral sensitivity in
glioblastoma cells can be explained by oxidative stress modulation because although resistant
due to P-gp expression, U87-TxR cells are more susceptible to changes in oxidative status
than U87 cells.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Evading multidrug resistance in glioblastoma with natural compound sclareol and its novel derivatives",
pages = "72",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5928"
}

Lupšić, E., Stepanović, A., Stojković, P., Terzić-Jpvanović, N., Novaković, M., Nedialkov, P., Trendafilova, A., Opsenica, I. M.,& Pešić, M.. (2023). Evading multidrug resistance in glioblastoma with natural compound sclareol and its novel derivatives. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 72.
https://hdl.handle.net/21.15107/rcub_ibiss_5928

Lupšić E, Stepanović A, Stojković P, Terzić-Jpvanović N, Novaković M, Nedialkov P, Trendafilova A, Opsenica IM, Pešić M. Evading multidrug resistance in glioblastoma with natural compound sclareol and its novel derivatives. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:72.
https://hdl.handle.net/21.15107/rcub_ibiss_5928 .

Lupšić, Ema, Stepanović, Ana, Stojković, Pavle, Terzić-Jpvanović, Nataša, Novaković, Miroslav, Nedialkov, Paraskev, Trendafilova, Antoaneta, Opsenica, Igor M., Pešić, Milica, "Evading multidrug resistance in glioblastoma with natural compound sclareol and its novel derivatives" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):72,
https://hdl.handle.net/21.15107/rcub_ibiss_5928 .

TY  - CONF
AU  - Stojković, Pavle A.
AU  - Stepanović, Ana
AU  - Lupšić, Ema
AU  - Terzić Jovanović, Nataša
AU  - Novaković, Miroslav
AU  - Pešić, Milica
AU  - Opsenica, Igor M.
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5911
AB  - Sklareol, biološki aktivan diterpen, je iskorišćen kao polazna supstanca za sintezu novih hibridnih molekula sa 1,2,4-triazolo[1,5-a]-pirimidinskim jezgrom (Slika 1). Svi derivati sklareola su testirani na ćelijsku liniju ljudskog glioblastoma U 7 i ćelijsku liniju U 7-TxR koja ispoljava višestruku rezistenciju na lekove. Jedinjenja su modifikovala aktivnost P-glikoproteina u sličnoj meri kao P-gp inhibitor treće generacije – tarikvidar. Ispitan je uticaj novih jedinjenja na različite ćelijske procese među kojima su ćelijski ciklus i ćelijska smrt, kao i na koncentraciju reaktivnih kiseoničnih i azotnih vrsta (ROS/RNS) u ćelijama glioblastoma i na potencijal membrane mitohondrija.
AB  - Sclareol, a biologically active diterpenoid, was used as the starting material for the synthesis of novel hybrid molecules containing the 1,2,4-triazolo[1,5-a]-pyrimidine moiety. All sclareol derivatives were tested on human glioblastoma U87 and multi-drug resistant U87-TxR cells. Hybrid compounds decreased P-gp activity to the same extent as a third generation P-gp inhibitor - tariquidar. We examined the effect of novel compounds on various cellular processes including the cell cycle and cell death, as well as their influence on the levels of reactive oxygen and nitrogen species (ROS/RNS) and mitochondrial membrane potential in glioblastoma cells.
PB  - Belgrade: Serbian Chemical Society
C3  - Book of Abstracts and Proceedings: 59th meeting of the Serbian Chemical Society; 2023 Jun 1-2; Novi Sad, Serbia
T1  - Sinteza i citotoksičnost novih derivata sklareola
T1  - Synthesis and cytotoxic activity of novel sclareol derivatives
SP  - 77
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5911
ER  - 

@conference{
author = "Stojković, Pavle A. and Stepanović, Ana and Lupšić, Ema and Terzić Jovanović, Nataša and Novaković, Miroslav and Pešić, Milica and Opsenica, Igor M.",
year = "2023",
abstract = "Sklareol, biološki aktivan diterpen, je iskorišćen kao polazna supstanca za sintezu novih hibridnih molekula sa 1,2,4-triazolo[1,5-a]-pirimidinskim jezgrom (Slika 1). Svi derivati sklareola su testirani na ćelijsku liniju ljudskog glioblastoma U 7 i ćelijsku liniju U 7-TxR koja ispoljava višestruku rezistenciju na lekove. Jedinjenja su modifikovala aktivnost P-glikoproteina u sličnoj meri kao P-gp inhibitor treće generacije – tarikvidar. Ispitan je uticaj novih jedinjenja na različite ćelijske procese među kojima su ćelijski ciklus i ćelijska smrt, kao i na koncentraciju reaktivnih kiseoničnih i azotnih vrsta (ROS/RNS) u ćelijama glioblastoma i na potencijal membrane mitohondrija., Sclareol, a biologically active diterpenoid, was used as the starting material for the synthesis of novel hybrid molecules containing the 1,2,4-triazolo[1,5-a]-pyrimidine moiety. All sclareol derivatives were tested on human glioblastoma U87 and multi-drug resistant U87-TxR cells. Hybrid compounds decreased P-gp activity to the same extent as a third generation P-gp inhibitor - tariquidar. We examined the effect of novel compounds on various cellular processes including the cell cycle and cell death, as well as their influence on the levels of reactive oxygen and nitrogen species (ROS/RNS) and mitochondrial membrane potential in glioblastoma cells.",
publisher = "Belgrade: Serbian Chemical Society",
journal = "Book of Abstracts and Proceedings: 59th meeting of the Serbian Chemical Society; 2023 Jun 1-2; Novi Sad, Serbia",
title = "Sinteza i citotoksičnost novih derivata sklareola, Synthesis and cytotoxic activity of novel sclareol derivatives",
pages = "77",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5911"
}

Stojković, P. A., Stepanović, A., Lupšić, E., Terzić Jovanović, N., Novaković, M., Pešić, M.,& Opsenica, I. M.. (2023). Sinteza i citotoksičnost novih derivata sklareola. in Book of Abstracts and Proceedings: 59th meeting of the Serbian Chemical Society; 2023 Jun 1-2; Novi Sad, Serbia
Belgrade: Serbian Chemical Society., 77.
https://hdl.handle.net/21.15107/rcub_ibiss_5911

Stojković PA, Stepanović A, Lupšić E, Terzić Jovanović N, Novaković M, Pešić M, Opsenica IM. Sinteza i citotoksičnost novih derivata sklareola. in Book of Abstracts and Proceedings: 59th meeting of the Serbian Chemical Society; 2023 Jun 1-2; Novi Sad, Serbia. 2023;:77.
https://hdl.handle.net/21.15107/rcub_ibiss_5911 .

Stojković, Pavle A., Stepanović, Ana, Lupšić, Ema, Terzić Jovanović, Nataša, Novaković, Miroslav, Pešić, Milica, Opsenica, Igor M., "Sinteza i citotoksičnost novih derivata sklareola" in Book of Abstracts and Proceedings: 59th meeting of the Serbian Chemical Society; 2023 Jun 1-2; Novi Sad, Serbia (2023):77,
https://hdl.handle.net/21.15107/rcub_ibiss_5911 .

TY  - JOUR
AU  - Stojković, Pavle
AU  - Stepanović, Ana
AU  - Lupšić, Ema
AU  - Terzić Jovanović, Nataša
AU  - Novaković, Miroslav
AU  - Nedialkov, Paraskev
AU  - Trendafilova, Antoaneta
AU  - Pešić, Milica
AU  - Opsenica, Igor M.
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5910
AB  - The synthesis of 24 hybrid molecules, consisting of naturally occurring sclareol (SCL) and synthetic 1,2,4-triazolo
[1,5-a]pyrimidines (TPs), is described. New compounds were designed with the aim of improving the cytotoxic
properties, activity, and selectivity of the parent compounds. Six analogs (12a-f) contained 4-benzylpiperazine
linkage, while 4-benzyldiamine linkage was present in eighteen derivatives (12g-r and 13a-f). Hybrids 13a-f
consist of two TP units. After purification, all hybrids (12a-r and 13a-f), as well as their precursors (9a-e and
11a-c), were tested on human glioblastoma U87 cells. More than half of the tested synthesized molecules, 16 out
of 31, caused a significant reduction of U87 cell viability (more than 75% reduction) at 30 μM. The
concentration-dependent cytotoxicity of these 16 compounds was also examined on U87 cells, corresponding
multidrug-resistant (MDR) U87-TxR cells with increased P-glycoprotein (P-gp) expression and activity, and
normal lung fibroblasts MRC-5. Importantly, 12l and 12r were active in the nanomolar range, while seven
compounds (11b, 11c, 12i, 12l, 12n, 12q, and 12r) were more selective towards glioblastoma cells than SCL. All
compounds except 12r evaded MDR, showing even better cytotoxicity in U87-TxR cells. In particular, 11c, 12a,
12g, 12j, 12k, 12m, 12n, and SCL showed collateral sensitivity. Hybrid compounds 12l, 12q, and 12r decreased
P-gp activity to the same extent as a well-known P-gp inhibitor - tariquidar (TQ). Hybrid compound 12l and its
precursor 11c affected different cellular processes including the cell cycle, cell death, and mitochondrial
membrane potential, and changed the levels of reactive oxygen and nitrogen species (ROS/RNS) in glioblastoma
cells. Collateral sensitivity towards MDR glioblastoma cells was caused by the modulation of oxidative stress
accompanied by inhibition of mitochondria.
PB  - Academic Press Inc.
T2  - Bioorganic Chemistry
T1  - Novel hybrids of sclareol and 1,2,4-triazolo[1,5-a]pyrimidine show collateral sensitivity in multidrug-resistant glioblastoma cells
VL  - 138
DO  - 10.1016/j.bioorg.2023.106605
SP  - 106605
ER  - 

@article{
author = "Stojković, Pavle and Stepanović, Ana and Lupšić, Ema and Terzić Jovanović, Nataša and Novaković, Miroslav and Nedialkov, Paraskev and Trendafilova, Antoaneta and Pešić, Milica and Opsenica, Igor M.",
year = "2023",
abstract = "The synthesis of 24 hybrid molecules, consisting of naturally occurring sclareol (SCL) and synthetic 1,2,4-triazolo
[1,5-a]pyrimidines (TPs), is described. New compounds were designed with the aim of improving the cytotoxic
properties, activity, and selectivity of the parent compounds. Six analogs (12a-f) contained 4-benzylpiperazine
linkage, while 4-benzyldiamine linkage was present in eighteen derivatives (12g-r and 13a-f). Hybrids 13a-f
consist of two TP units. After purification, all hybrids (12a-r and 13a-f), as well as their precursors (9a-e and
11a-c), were tested on human glioblastoma U87 cells. More than half of the tested synthesized molecules, 16 out
of 31, caused a significant reduction of U87 cell viability (more than 75% reduction) at 30 μM. The
concentration-dependent cytotoxicity of these 16 compounds was also examined on U87 cells, corresponding
multidrug-resistant (MDR) U87-TxR cells with increased P-glycoprotein (P-gp) expression and activity, and
normal lung fibroblasts MRC-5. Importantly, 12l and 12r were active in the nanomolar range, while seven
compounds (11b, 11c, 12i, 12l, 12n, 12q, and 12r) were more selective towards glioblastoma cells than SCL. All
compounds except 12r evaded MDR, showing even better cytotoxicity in U87-TxR cells. In particular, 11c, 12a,
12g, 12j, 12k, 12m, 12n, and SCL showed collateral sensitivity. Hybrid compounds 12l, 12q, and 12r decreased
P-gp activity to the same extent as a well-known P-gp inhibitor - tariquidar (TQ). Hybrid compound 12l and its
precursor 11c affected different cellular processes including the cell cycle, cell death, and mitochondrial
membrane potential, and changed the levels of reactive oxygen and nitrogen species (ROS/RNS) in glioblastoma
cells. Collateral sensitivity towards MDR glioblastoma cells was caused by the modulation of oxidative stress
accompanied by inhibition of mitochondria.",
publisher = "Academic Press Inc.",
journal = "Bioorganic Chemistry",
title = "Novel hybrids of sclareol and 1,2,4-triazolo[1,5-a]pyrimidine show collateral sensitivity in multidrug-resistant glioblastoma cells",
volume = "138",
doi = "10.1016/j.bioorg.2023.106605",
pages = "106605"
}

Stojković, P., Stepanović, A., Lupšić, E., Terzić Jovanović, N., Novaković, M., Nedialkov, P., Trendafilova, A., Pešić, M.,& Opsenica, I. M.. (2023). Novel hybrids of sclareol and 1,2,4-triazolo[1,5-a]pyrimidine show collateral sensitivity in multidrug-resistant glioblastoma cells. in Bioorganic Chemistry
Academic Press Inc.., 138, 106605.
https://doi.org/10.1016/j.bioorg.2023.106605

Stojković P, Stepanović A, Lupšić E, Terzić Jovanović N, Novaković M, Nedialkov P, Trendafilova A, Pešić M, Opsenica IM. Novel hybrids of sclareol and 1,2,4-triazolo[1,5-a]pyrimidine show collateral sensitivity in multidrug-resistant glioblastoma cells. in Bioorganic Chemistry. 2023;138:106605.
doi:10.1016/j.bioorg.2023.106605 .

Stojković, Pavle, Stepanović, Ana, Lupšić, Ema, Terzić Jovanović, Nataša, Novaković, Miroslav, Nedialkov, Paraskev, Trendafilova, Antoaneta, Pešić, Milica, Opsenica, Igor M., "Novel hybrids of sclareol and 1,2,4-triazolo[1,5-a]pyrimidine show collateral sensitivity in multidrug-resistant glioblastoma cells" in Bioorganic Chemistry, 138 (2023):106605,
https://doi.org/10.1016/j.bioorg.2023.106605 . .

TY  - JOUR
AU  - Koračak, Ljiljana
AU  - Lupšić, Ema
AU  - Terzić Jovanović, Nataša
AU  - Jovanović, Mirna
AU  - Novaković, Miroslav
AU  - Nedialkov, Paraskev
AU  - Trendafilova, Antoaneta
AU  - Zlatović, Mario
AU  - Pešić, Milica
AU  - Opsenica, Igor
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5890
AB  - The synthesis of 17 hybrid molecules, consisting of artesunate, a derivative of naturally occurring artemisinin, and synthetic 4-aryl-2-aminopyrimidines, is described. New compounds were designed to improve the parent compounds' cytotoxic properties, activity, and selectivity. The synthesized hybrid molecules (15a–f with ethylenediamine linker and 16a–k with piperazine linker), as well as their precursors – pyrimidine derivatives (13a–f and 14a–k), artemisinin, and artesunate, were tested on sensitive and multidrug-resistant (MDR) human non-small cell lung carcinoma (NSCLC) cells. All hybrid compounds with piperazine linker 16a–k were selective toward NSCLC cells and displayed IC50 values below 5 μM. Although they showed similar anticancer potency as artesunate, their selectivity against cancer cells was considerably improved. Importantly, 16h–k hybrid compounds were able to evade MDR phenotype, inhibit P-glycoprotein (P-gp) activity, and increase the sensitivity of MDR NSCLC cells to doxorubicin (DOX). The inhibition of P-gp activity induced by 16h–j was stronger than the one obtained with artesunate. Among these four hybrid compounds, 16k was the most potent anticancer agent with similar IC50 values of around 1.5 μM (for comparison – over 3.1 μM for artesunate) in sensitive and MDR NSCLC cells.
PB  - Cambridge: Royal Society of Chemistry
T2  - New Journal of Chemistry
T1  - Novel artesunate–pyrimidine-based hybrids with anticancer potential against multidrug-resistant cancer cells
IS  - 14
VL  - 47
DO  - 10.1039/D3NJ00427A
SP  - 6844
EP  - 6855
ER  - 

@article{
author = "Koračak, Ljiljana and Lupšić, Ema and Terzić Jovanović, Nataša and Jovanović, Mirna and Novaković, Miroslav and Nedialkov, Paraskev and Trendafilova, Antoaneta and Zlatović, Mario and Pešić, Milica and Opsenica, Igor",
year = "2023",
abstract = "The synthesis of 17 hybrid molecules, consisting of artesunate, a derivative of naturally occurring artemisinin, and synthetic 4-aryl-2-aminopyrimidines, is described. New compounds were designed to improve the parent compounds' cytotoxic properties, activity, and selectivity. The synthesized hybrid molecules (15a–f with ethylenediamine linker and 16a–k with piperazine linker), as well as their precursors – pyrimidine derivatives (13a–f and 14a–k), artemisinin, and artesunate, were tested on sensitive and multidrug-resistant (MDR) human non-small cell lung carcinoma (NSCLC) cells. All hybrid compounds with piperazine linker 16a–k were selective toward NSCLC cells and displayed IC50 values below 5 μM. Although they showed similar anticancer potency as artesunate, their selectivity against cancer cells was considerably improved. Importantly, 16h–k hybrid compounds were able to evade MDR phenotype, inhibit P-glycoprotein (P-gp) activity, and increase the sensitivity of MDR NSCLC cells to doxorubicin (DOX). The inhibition of P-gp activity induced by 16h–j was stronger than the one obtained with artesunate. Among these four hybrid compounds, 16k was the most potent anticancer agent with similar IC50 values of around 1.5 μM (for comparison – over 3.1 μM for artesunate) in sensitive and MDR NSCLC cells.",
publisher = "Cambridge: Royal Society of Chemistry",
journal = "New Journal of Chemistry",
title = "Novel artesunate–pyrimidine-based hybrids with anticancer potential against multidrug-resistant cancer cells",
number = "14",
volume = "47",
doi = "10.1039/D3NJ00427A",
pages = "6844-6855"
}

Koračak, L., Lupšić, E., Terzić Jovanović, N., Jovanović, M., Novaković, M., Nedialkov, P., Trendafilova, A., Zlatović, M., Pešić, M.,& Opsenica, I.. (2023). Novel artesunate–pyrimidine-based hybrids with anticancer potential against multidrug-resistant cancer cells. in New Journal of Chemistry
Cambridge: Royal Society of Chemistry., 47(14), 6844-6855.
https://doi.org/10.1039/D3NJ00427A

Koračak L, Lupšić E, Terzić Jovanović N, Jovanović M, Novaković M, Nedialkov P, Trendafilova A, Zlatović M, Pešić M, Opsenica I. Novel artesunate–pyrimidine-based hybrids with anticancer potential against multidrug-resistant cancer cells. in New Journal of Chemistry. 2023;47(14):6844-6855.
doi:10.1039/D3NJ00427A .

Koračak, Ljiljana, Lupšić, Ema, Terzić Jovanović, Nataša, Jovanović, Mirna, Novaković, Miroslav, Nedialkov, Paraskev, Trendafilova, Antoaneta, Zlatović, Mario, Pešić, Milica, Opsenica, Igor, "Novel artesunate–pyrimidine-based hybrids with anticancer potential against multidrug-resistant cancer cells" in New Journal of Chemistry, 47, no. 14 (2023):6844-6855,
https://doi.org/10.1039/D3NJ00427A . .

TY  - CONF
AU  - Stojković, Pavle
AU  - Stepanović, Ana
AU  - Terzić Jovanović, Nataša
AU  - Novaković, Miroslav
AU  - Trendafilova, Antoaneta
AU  - Pešić, Milica
AU  - Opsenica, Igor M.
PY  - 2022
UR  - https://euchems2022.eu/images/abstracts.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5372
AB  - Sclareol is a labdane diterpenoid found in clary sage (Salvia sclarea L.) with various biological activities,
most notably anticancer and cytotoxic activity [1]. There are several examples of synthetic derivatives
of sclareol with antischistosomal [2], antifungal [3], and anticancer activity [4]. Since it is known that
modifications of biologically active molecules can lead to the improvement of physicochemical
properties and modes of interactions with target cells, we have envisioned the derivatization of sclareol
to obtain molecules with more potent cytotoxic activity.
Sclareol used as a starting material in this research was isolated from Clary sage harvested in Bulgaria.
New compounds were obtained by derivatization of sclareol at its Δ14,15 double bond using oxidative
Heck coupling catalyzed by palladium-acetate with copper(II)-acetate as oxidant, followed by the
introduction of different diamine-moieties. Finally, the terminal amino-group was coupled with a
nitrogen-rich heterocycle to obtain desired compounds. During the course of the synthesis, both tertiary
and tertiary allylic hydroxyl groups remained unchanged, which was of particular interest, since it was
shown that the tertiary allylic group is crucial for the biological activity of sclareol.
Synthesized compounds were tested on human cancer cell lines, primarily glioblastoma cells. It was
shown that certain derivatives have caused a significant reduction of glioblastoma cell viability at low
concentrations. Moreover, some derivatives inhibited cell membrane transporter P-glycoprotein (P-gp)
responsible for multidrug resistance and increased accumulation of doxorubicin to the same extent as
tariquidar (a well-known P-gp inhibitor). Most importantly, novel molecules exhibited more potent
biological activity than sclareol itself.
PB  - Sociedade Portuguesa de Química
C3  - Abstract Book: 8th EuChemS Chemistry Congress; 2022 Aug 28 - Sep 1; Lisbon, Portugal
T1  - Synthesis of novel sclareol derivatives and evaluation of their anticancer activity
SP  - 604
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5372
ER  - 

@conference{
author = "Stojković, Pavle and Stepanović, Ana and Terzić Jovanović, Nataša and Novaković, Miroslav and Trendafilova, Antoaneta and Pešić, Milica and Opsenica, Igor M.",
year = "2022",
abstract = "Sclareol is a labdane diterpenoid found in clary sage (Salvia sclarea L.) with various biological activities,
most notably anticancer and cytotoxic activity [1]. There are several examples of synthetic derivatives
of sclareol with antischistosomal [2], antifungal [3], and anticancer activity [4]. Since it is known that
modifications of biologically active molecules can lead to the improvement of physicochemical
properties and modes of interactions with target cells, we have envisioned the derivatization of sclareol
to obtain molecules with more potent cytotoxic activity.
Sclareol used as a starting material in this research was isolated from Clary sage harvested in Bulgaria.
New compounds were obtained by derivatization of sclareol at its Δ14,15 double bond using oxidative
Heck coupling catalyzed by palladium-acetate with copper(II)-acetate as oxidant, followed by the
introduction of different diamine-moieties. Finally, the terminal amino-group was coupled with a
nitrogen-rich heterocycle to obtain desired compounds. During the course of the synthesis, both tertiary
and tertiary allylic hydroxyl groups remained unchanged, which was of particular interest, since it was
shown that the tertiary allylic group is crucial for the biological activity of sclareol.
Synthesized compounds were tested on human cancer cell lines, primarily glioblastoma cells. It was
shown that certain derivatives have caused a significant reduction of glioblastoma cell viability at low
concentrations. Moreover, some derivatives inhibited cell membrane transporter P-glycoprotein (P-gp)
responsible for multidrug resistance and increased accumulation of doxorubicin to the same extent as
tariquidar (a well-known P-gp inhibitor). Most importantly, novel molecules exhibited more potent
biological activity than sclareol itself.",
publisher = "Sociedade Portuguesa de Química",
journal = "Abstract Book: 8th EuChemS Chemistry Congress; 2022 Aug 28 - Sep 1; Lisbon, Portugal",
title = "Synthesis of novel sclareol derivatives and evaluation of their anticancer activity",
pages = "604",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5372"
}

Stojković, P., Stepanović, A., Terzić Jovanović, N., Novaković, M., Trendafilova, A., Pešić, M.,& Opsenica, I. M.. (2022). Synthesis of novel sclareol derivatives and evaluation of their anticancer activity. in Abstract Book: 8th EuChemS Chemistry Congress; 2022 Aug 28 - Sep 1; Lisbon, Portugal
Sociedade Portuguesa de Química., 604.
https://hdl.handle.net/21.15107/rcub_ibiss_5372

Stojković P, Stepanović A, Terzić Jovanović N, Novaković M, Trendafilova A, Pešić M, Opsenica IM. Synthesis of novel sclareol derivatives and evaluation of their anticancer activity. in Abstract Book: 8th EuChemS Chemistry Congress; 2022 Aug 28 - Sep 1; Lisbon, Portugal. 2022;:604.
https://hdl.handle.net/21.15107/rcub_ibiss_5372 .

Stojković, Pavle, Stepanović, Ana, Terzić Jovanović, Nataša, Novaković, Miroslav, Trendafilova, Antoaneta, Pešić, Milica, Opsenica, Igor M., "Synthesis of novel sclareol derivatives and evaluation of their anticancer activity" in Abstract Book: 8th EuChemS Chemistry Congress; 2022 Aug 28 - Sep 1; Lisbon, Portugal (2022):604,
https://hdl.handle.net/21.15107/rcub_ibiss_5372 .

TY  - CONF
AU  - Stepanović, Ana
AU  - Stojković, Pavle
AU  - Terzić Jovanović, Nataša
AU  - Novaković, Miroslav
AU  - Opsenica, Igor M.
AU  - Pešić, Milica
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5370
AB  - Background: Natural products exhibit a wide range of biological activities and they are starting point in the drug discovery process. Sclareol (SCL) naturally occurring labdane diterpene isolated from Clary sage (Salvia sclarea L.) shows diverse biological properties such as antioxidative, antimicrobial, anti-inflammatory, and anticancer activities. It is well established that fusing two pharmacophores can lead to significant improvement in the biological potential of the molecule by modifying its physicochemical properties. We envisioned that chimeric molecules synthesized by linking triazolo[1,5-a]pyrimidine pharmacophore to SCL would have more potent anticancer activity than their parental compound – SCL. Therefore, the cytotoxic potential of a series of SCL derivatives was compared with SCL. We have also studied their potential to increase the accumulation of substrates of membrane transporter which causes resistance of cancer cells – P-glycoprotein (P-gp). Methods: Cytotoxic potential, selectivity towards cancer cells, and resistance profile of SCL and its derivatives were examined by MTT assay after 72 h exposure in human glioblastoma cells (sensitive U87 and multidrug-resistant U87-TxR) and rat microglial cells (BV-2). We also investigated the effect of SCL and its derivatives on P-gp activity in U87-TxR resistant cells by determining the level of accumulated P-gp substrates (rhodamine 123 and doxorubicin) by flow cytometry. Results: More than half of the tested SCL derivatives considerably reduced glioblastoma cell viability with a concentration of 5 μM. Tested compounds evaded the resistance of glioblastoma cells showing similar or better activity against U87-TxR cells in comparison with U87 cells. All compounds significantly increased the accumulation of rhodamine 123 pointing to the inhibition of P-gp. However, only three of them increased the accumulation of doxorubicin likewise tariquidar, a well-known third-generation P-gp inhibitor, implying that these three SCL derivatives can be valuable as chemo-sensitizing agents. Conclusion: Our results showed that SCL derivatives can be considered as modulators of P-gp activity especially pointing to several lead compounds whose detailed molecular mechanism of anticancer action should be studied.
PB  - STRATAGEM COST Action
C3  - Abstract Book: STRATAGEM’s 5th Annual Meeting: New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumours; 2022 Jun 29 - Jul 1; Coimbra, Portugal
T1  - Hybrids of sclareol and 1,2,4-triazolo[1,5-a]pyrimidine inhibit P-glycoprotein function in glioblastoma cells
SP  - 81
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5370
ER  - 

@conference{
author = "Stepanović, Ana and Stojković, Pavle and Terzić Jovanović, Nataša and Novaković, Miroslav and Opsenica, Igor M. and Pešić, Milica",
year = "2022",
abstract = "Background: Natural products exhibit a wide range of biological activities and they are starting point in the drug discovery process. Sclareol (SCL) naturally occurring labdane diterpene isolated from Clary sage (Salvia sclarea L.) shows diverse biological properties such as antioxidative, antimicrobial, anti-inflammatory, and anticancer activities. It is well established that fusing two pharmacophores can lead to significant improvement in the biological potential of the molecule by modifying its physicochemical properties. We envisioned that chimeric molecules synthesized by linking triazolo[1,5-a]pyrimidine pharmacophore to SCL would have more potent anticancer activity than their parental compound – SCL. Therefore, the cytotoxic potential of a series of SCL derivatives was compared with SCL. We have also studied their potential to increase the accumulation of substrates of membrane transporter which causes resistance of cancer cells – P-glycoprotein (P-gp). Methods: Cytotoxic potential, selectivity towards cancer cells, and resistance profile of SCL and its derivatives were examined by MTT assay after 72 h exposure in human glioblastoma cells (sensitive U87 and multidrug-resistant U87-TxR) and rat microglial cells (BV-2). We also investigated the effect of SCL and its derivatives on P-gp activity in U87-TxR resistant cells by determining the level of accumulated P-gp substrates (rhodamine 123 and doxorubicin) by flow cytometry. Results: More than half of the tested SCL derivatives considerably reduced glioblastoma cell viability with a concentration of 5 μM. Tested compounds evaded the resistance of glioblastoma cells showing similar or better activity against U87-TxR cells in comparison with U87 cells. All compounds significantly increased the accumulation of rhodamine 123 pointing to the inhibition of P-gp. However, only three of them increased the accumulation of doxorubicin likewise tariquidar, a well-known third-generation P-gp inhibitor, implying that these three SCL derivatives can be valuable as chemo-sensitizing agents. Conclusion: Our results showed that SCL derivatives can be considered as modulators of P-gp activity especially pointing to several lead compounds whose detailed molecular mechanism of anticancer action should be studied.",
publisher = "STRATAGEM COST Action",
journal = "Abstract Book: STRATAGEM’s 5th Annual Meeting: New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumours; 2022 Jun 29 - Jul 1; Coimbra, Portugal",
title = "Hybrids of sclareol and 1,2,4-triazolo[1,5-a]pyrimidine inhibit P-glycoprotein function in glioblastoma cells",
pages = "81",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5370"
}

Stepanović, A., Stojković, P., Terzić Jovanović, N., Novaković, M., Opsenica, I. M.,& Pešić, M.. (2022). Hybrids of sclareol and 1,2,4-triazolo[1,5-a]pyrimidine inhibit P-glycoprotein function in glioblastoma cells. in Abstract Book: STRATAGEM’s 5th Annual Meeting: New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumours; 2022 Jun 29 - Jul 1; Coimbra, Portugal
STRATAGEM COST Action., 81.
https://hdl.handle.net/21.15107/rcub_ibiss_5370

Stepanović A, Stojković P, Terzić Jovanović N, Novaković M, Opsenica IM, Pešić M. Hybrids of sclareol and 1,2,4-triazolo[1,5-a]pyrimidine inhibit P-glycoprotein function in glioblastoma cells. in Abstract Book: STRATAGEM’s 5th Annual Meeting: New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumours; 2022 Jun 29 - Jul 1; Coimbra, Portugal. 2022;:81.
https://hdl.handle.net/21.15107/rcub_ibiss_5370 .

Stepanović, Ana, Stojković, Pavle, Terzić Jovanović, Nataša, Novaković, Miroslav, Opsenica, Igor M., Pešić, Milica, "Hybrids of sclareol and 1,2,4-triazolo[1,5-a]pyrimidine inhibit P-glycoprotein function in glioblastoma cells" in Abstract Book: STRATAGEM’s 5th Annual Meeting: New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumours; 2022 Jun 29 - Jul 1; Coimbra, Portugal (2022):81,
https://hdl.handle.net/21.15107/rcub_ibiss_5370 .

TY  - CONF
AU  - Lupšić, Ema
AU  - Stepanović, Ana
AU  - Nikolić, Andrea M.
AU  - Dragoj, Miodrag
AU  - Jovanović Stojanov, Sofija
AU  - Novaković, Miroslav
AU  - Opsenica, Igor M.
AU  - Pešić, Milica
PY  - 2021
UR  - https://stratagem-cost.eu/2021/09/stratagems-4th-annual-conference-in-prague-czechia-to-take-place-on/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5957
AB  - Multidrug resistance (MDR) is one of the major obstacles to successful cancer treatment. How to
overcome cancer MDR is still an unsolved issue in clinical practice although several generations of MDR
transporters’ inhibitors have been developed and widely investigated so far. Nature is an important source
of potential anticancer agents capable to suppress the activity of membrane transporters implicated in MDR
such as P-glycoprotein (P-gp). In this study, we evaluated the effects of sclareol (SC), a naturally occurring
labdane type diterpene, on the P-gp activity and its potential to sensitize different human cancer cell lines
to doxorubicin (DOX). To that end, we used several human cancer cell lines (colorectal carcinoma, DLD1,
and its MDR variant DLD1-TxR, non-small cell lung carcinoma NCI-H460, and its MDR variant NCIH460/R, glioblastoma U251, U87, and its MDR variant U87-TxR) and normal human embryonic lung fibroblasts (MRC-5). The effects of SC alone and in combination with DOX on cell viability were assessed by
MTT, while the effects on DOX and rhodamine 123 (Rho 123) accumulation as determinants of P-gp activity
were assessed by flow cytometry. The efficient concentrations of SC that significantly decreased cell viability
(IC50 values) ranged between 20 µM for DLD1 and 60 µM for MRC-5. The presence of MDR phenotype did
not diminish the SC effect on cell viability, even more, SC was more potent in U87-TxR than in U87 cells.
The effects of 72 h simultaneous treatment of SC (10 and 20 µM) with DOX (20, 50, 100, 200 and 500 nM)
demonstrated the considerable potential of SC to sensitize DLD1, DLD1-TxR, NCI-H460/R, U87-TxR and
U251 cells to DOX. However, the observed sensitization was not due to the P-gp inhibition in all MDR cancer
cell lines. Only in NCI-H460/R the obvious suppression of P-gp was observed due to the significant increase
in the accumulation of both P-gp substrates (DOX and Rho 123). SC did not affect the P-gp activity in DLD1
and DLD1-TxR cells. On the contrary, DOX and Rho123 accumulation increased in U87 and U87-TxR albeit
the fact that U87 cells do not express P-gp. Results obtained in this study showed a considerable potential
of SC to sensitize cancer cells to DOX. However, the effects of SC are cancer type-specific and not solely
dependent on the suppression of P-gp activity. Further investigations are envisioned to determine molecular
mechanisms of SC in different cancer cell types.
PB  - STRATAGEM
C3  - 4th Annual STRATAGEM Conference: New Diagnostic and therapeutic tools against multidrug resistant tumours; 2021 Sep 6-8; Prague; Czechia
T1  - Sclareol, a fragrant natural compound, suppresses P-glycoprotein activity and sensitizes resistant cancer cells to doxorubicin
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5957
ER  - 

@conference{
author = "Lupšić, Ema and Stepanović, Ana and Nikolić, Andrea M. and Dragoj, Miodrag and Jovanović Stojanov, Sofija and Novaković, Miroslav and Opsenica, Igor M. and Pešić, Milica",
year = "2021",
abstract = "Multidrug resistance (MDR) is one of the major obstacles to successful cancer treatment. How to
overcome cancer MDR is still an unsolved issue in clinical practice although several generations of MDR
transporters’ inhibitors have been developed and widely investigated so far. Nature is an important source
of potential anticancer agents capable to suppress the activity of membrane transporters implicated in MDR
such as P-glycoprotein (P-gp). In this study, we evaluated the effects of sclareol (SC), a naturally occurring
labdane type diterpene, on the P-gp activity and its potential to sensitize different human cancer cell lines
to doxorubicin (DOX). To that end, we used several human cancer cell lines (colorectal carcinoma, DLD1,
and its MDR variant DLD1-TxR, non-small cell lung carcinoma NCI-H460, and its MDR variant NCIH460/R, glioblastoma U251, U87, and its MDR variant U87-TxR) and normal human embryonic lung fibroblasts (MRC-5). The effects of SC alone and in combination with DOX on cell viability were assessed by
MTT, while the effects on DOX and rhodamine 123 (Rho 123) accumulation as determinants of P-gp activity
were assessed by flow cytometry. The efficient concentrations of SC that significantly decreased cell viability
(IC50 values) ranged between 20 µM for DLD1 and 60 µM for MRC-5. The presence of MDR phenotype did
not diminish the SC effect on cell viability, even more, SC was more potent in U87-TxR than in U87 cells.
The effects of 72 h simultaneous treatment of SC (10 and 20 µM) with DOX (20, 50, 100, 200 and 500 nM)
demonstrated the considerable potential of SC to sensitize DLD1, DLD1-TxR, NCI-H460/R, U87-TxR and
U251 cells to DOX. However, the observed sensitization was not due to the P-gp inhibition in all MDR cancer
cell lines. Only in NCI-H460/R the obvious suppression of P-gp was observed due to the significant increase
in the accumulation of both P-gp substrates (DOX and Rho 123). SC did not affect the P-gp activity in DLD1
and DLD1-TxR cells. On the contrary, DOX and Rho123 accumulation increased in U87 and U87-TxR albeit
the fact that U87 cells do not express P-gp. Results obtained in this study showed a considerable potential
of SC to sensitize cancer cells to DOX. However, the effects of SC are cancer type-specific and not solely
dependent on the suppression of P-gp activity. Further investigations are envisioned to determine molecular
mechanisms of SC in different cancer cell types.",
publisher = "STRATAGEM",
journal = "4th Annual STRATAGEM Conference: New Diagnostic and therapeutic tools against multidrug resistant tumours; 2021 Sep 6-8; Prague; Czechia",
title = "Sclareol, a fragrant natural compound, suppresses P-glycoprotein activity and sensitizes resistant cancer cells to doxorubicin",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5957"
}

Lupšić, E., Stepanović, A., Nikolić, A. M., Dragoj, M., Jovanović Stojanov, S., Novaković, M., Opsenica, I. M.,& Pešić, M.. (2021). Sclareol, a fragrant natural compound, suppresses P-glycoprotein activity and sensitizes resistant cancer cells to doxorubicin. in 4th Annual STRATAGEM Conference: New Diagnostic and therapeutic tools against multidrug resistant tumours; 2021 Sep 6-8; Prague; Czechia
STRATAGEM..
https://hdl.handle.net/21.15107/rcub_ibiss_5957

Lupšić E, Stepanović A, Nikolić AM, Dragoj M, Jovanović Stojanov S, Novaković M, Opsenica IM, Pešić M. Sclareol, a fragrant natural compound, suppresses P-glycoprotein activity and sensitizes resistant cancer cells to doxorubicin. in 4th Annual STRATAGEM Conference: New Diagnostic and therapeutic tools against multidrug resistant tumours; 2021 Sep 6-8; Prague; Czechia. 2021;.
https://hdl.handle.net/21.15107/rcub_ibiss_5957 .

Lupšić, Ema, Stepanović, Ana, Nikolić, Andrea M., Dragoj, Miodrag, Jovanović Stojanov, Sofija, Novaković, Miroslav, Opsenica, Igor M., Pešić, Milica, "Sclareol, a fragrant natural compound, suppresses P-glycoprotein activity and sensitizes resistant cancer cells to doxorubicin" in 4th Annual STRATAGEM Conference: New Diagnostic and therapeutic tools against multidrug resistant tumours; 2021 Sep 6-8; Prague; Czechia (2021),
https://hdl.handle.net/21.15107/rcub_ibiss_5957 .

TY  - CONF
AU  - Stepanović, Ana
AU  - Lupšić, Ema
AU  - Stojković, Pavle
AU  - Dragoj, Miodrag
AU  - Jovanović Stojanov, Sofija
AU  - Terzić- Jovanović, Nataša
AU  - Novaković, Miroslav
AU  - Opsenica, Igor M.
AU  - Pešić, Milica
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4995
AB  - Background: Glioblastoma is the most common, aggressive and lethal brain tumor in adults with high proliferation rate, infiltrating nature and presence of multidrug resistance (MDR). Sclareol (SC) is a naturally occurring labdane type diterpene, derived from Salvia sclarea. We examined cell growth inhibition effect of SC and its derivatives (PAS and TNT groups of compounds) - hybrid (chimeric) molecules. Sclareol was covalently bonded to [1,2,4]triazolo[1,5-a]pyrimidin-7-amine scaffold, and different diamines were used as linkers. We also studied SC potential to reverse DOX resistance and its accumulation. The combination of SC with DOX has been earlier described to potentiate DOX cytotoxicity if simultaneously delivered in nanoparticles. Material and Methods: SC in combination with DOX as well as SC derivatives were tested on human glioma cell line U87, and its MDR counterpart - U87-TxR. MTT assay was used to examine inhibition of cell growth. Accumulation of DOX was measured by flow cytometry. Results: Thirteen out of nineteen TNT derivatives and three out of six PAS derivatives showed stronger anti-glioma effect than SC. Simultaneous treatment of SC with DOX demonstrated potential of SC to reverse DOX resistance. Even more, SC significantly increased DOX accumulation in both glioblastoma cell lines. Conclusion: Results obtained in this study showed a considerable synergy of SC and DOX in glioma cells. Better results observed with SC derivatives make them good candidates for further testing.
PB  - Belgrade: Serbian Association for Cancer Research
C3  - Abstract book: The fifth congress of the Serbian association for cancer research:“Translational potential of cancer research in Serbia“; 2021 Dec 3; Virtual.
T1  - Anticancer effects of sclareol and its derivatives in glioblastoma cells
SP  - 72
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4995
ER  - 

@conference{
author = "Stepanović, Ana and Lupšić, Ema and Stojković, Pavle and Dragoj, Miodrag and Jovanović Stojanov, Sofija and Terzić- Jovanović, Nataša and Novaković, Miroslav and Opsenica, Igor M. and Pešić, Milica",
year = "2021",
abstract = "Background: Glioblastoma is the most common, aggressive and lethal brain tumor in adults with high proliferation rate, infiltrating nature and presence of multidrug resistance (MDR). Sclareol (SC) is a naturally occurring labdane type diterpene, derived from Salvia sclarea. We examined cell growth inhibition effect of SC and its derivatives (PAS and TNT groups of compounds) - hybrid (chimeric) molecules. Sclareol was covalently bonded to [1,2,4]triazolo[1,5-a]pyrimidin-7-amine scaffold, and different diamines were used as linkers. We also studied SC potential to reverse DOX resistance and its accumulation. The combination of SC with DOX has been earlier described to potentiate DOX cytotoxicity if simultaneously delivered in nanoparticles. Material and Methods: SC in combination with DOX as well as SC derivatives were tested on human glioma cell line U87, and its MDR counterpart - U87-TxR. MTT assay was used to examine inhibition of cell growth. Accumulation of DOX was measured by flow cytometry. Results: Thirteen out of nineteen TNT derivatives and three out of six PAS derivatives showed stronger anti-glioma effect than SC. Simultaneous treatment of SC with DOX demonstrated potential of SC to reverse DOX resistance. Even more, SC significantly increased DOX accumulation in both glioblastoma cell lines. Conclusion: Results obtained in this study showed a considerable synergy of SC and DOX in glioma cells. Better results observed with SC derivatives make them good candidates for further testing.",
publisher = "Belgrade: Serbian Association for Cancer Research",
journal = "Abstract book: The fifth congress of the Serbian association for cancer research:“Translational potential of cancer research in Serbia“; 2021 Dec 3; Virtual.",
title = "Anticancer effects of sclareol and its derivatives in glioblastoma cells",
pages = "72",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4995"
}

Stepanović, A., Lupšić, E., Stojković, P., Dragoj, M., Jovanović Stojanov, S., Terzić- Jovanović, N., Novaković, M., Opsenica, I. M.,& Pešić, M.. (2021). Anticancer effects of sclareol and its derivatives in glioblastoma cells. in Abstract book: The fifth congress of the Serbian association for cancer research:“Translational potential of cancer research in Serbia“; 2021 Dec 3; Virtual.
Belgrade: Serbian Association for Cancer Research., 72.
https://hdl.handle.net/21.15107/rcub_ibiss_4995

Stepanović A, Lupšić E, Stojković P, Dragoj M, Jovanović Stojanov S, Terzić- Jovanović N, Novaković M, Opsenica IM, Pešić M. Anticancer effects of sclareol and its derivatives in glioblastoma cells. in Abstract book: The fifth congress of the Serbian association for cancer research:“Translational potential of cancer research in Serbia“; 2021 Dec 3; Virtual.. 2021;:72.
https://hdl.handle.net/21.15107/rcub_ibiss_4995 .

Stepanović, Ana, Lupšić, Ema, Stojković, Pavle, Dragoj, Miodrag, Jovanović Stojanov, Sofija, Terzić- Jovanović, Nataša, Novaković, Miroslav, Opsenica, Igor M., Pešić, Milica, "Anticancer effects of sclareol and its derivatives in glioblastoma cells" in Abstract book: The fifth congress of the Serbian association for cancer research:“Translational potential of cancer research in Serbia“; 2021 Dec 3; Virtual. (2021):72,
https://hdl.handle.net/21.15107/rcub_ibiss_4995 .

TY  - CONF
AU  - Stepanović, Ana
AU  - Lupšić, Ema
AU  - Nikolić, Andrea M.
AU  - Dragoj, Miodrag
AU  - Jovanović Stojanov, Sofija
AU  - Novaković, Miroslav
AU  - Opsenica, Igor M.
AU  - Pešić, Milica
PY  - 2021
UR  - http://www.bds.org.rs/download/SBS_Conference_10_2021.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5607
AB  - P-glycoprotein (P-gp) is often expressed at the cellular membrane of cancer cells where it plays a significant role in protecting cancer cells from extracellular assault. It works as an export transporter for many substrates - xenobiotics including chemotherapeutics. Several generations of P-gp inhibitors have been developed and studied but they have not yet been introduced into clinics. The most promising fourth-generation comprises natural compounds. In this study, we evaluated the potential of sclareol, a naturally occurring labdane diterpene, to inhibit P-gp activity in human glioblastoma (U87, and its resistant variant U87-TxR with P-gp overexpression) and non-small cell lung carcinoma (NCI-H460, and its resistant variant NCI-H460/R with P-gp overexpression) cell lines. To that end, we used the accumulation assays of fluorescent P-gp substrates (rhodamine 123 and doxorubicin) that were analyzed by flow cytometry. An increase in the accumulation of the P-gp substrate corresponds to the level of P-gp activity suppression. Our results showed that simultaneous application of sclareol (20 μM and 50 μM) with either rhodamine 123 (5 μM) or doxorubicin (20 μM) significantly increased their accumulation in resistant cells (U87-TxR and NCI-H460/R) than in their corresponding sensitive cells (U87 and NCI-H460). The doxorubicin accumulation was also considerably increased in sensitive U87 cells implying that sclareol may interact with doxorubicin through other mechanisms in glioblastoma cells (not only by P-gp inhibition). Further investigations are envisioned to reveal the mechanisms behind sclareol and doxorubicin interaction in glioblastoma cells.
PB  - Belgrade: Faculty of Chemistry: Serbian Biochemical Society, 2021
C3  - Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
T1  - Sclareol, a natural compound, inhibits P-glycoprotein activity in cancer cells
SP  - 77
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5607
ER  - 

@conference{
author = "Stepanović, Ana and Lupšić, Ema and Nikolić, Andrea M. and Dragoj, Miodrag and Jovanović Stojanov, Sofija and Novaković, Miroslav and Opsenica, Igor M. and Pešić, Milica",
year = "2021",
abstract = "P-glycoprotein (P-gp) is often expressed at the cellular membrane of cancer cells where it plays a significant role in protecting cancer cells from extracellular assault. It works as an export transporter for many substrates - xenobiotics including chemotherapeutics. Several generations of P-gp inhibitors have been developed and studied but they have not yet been introduced into clinics. The most promising fourth-generation comprises natural compounds. In this study, we evaluated the potential of sclareol, a naturally occurring labdane diterpene, to inhibit P-gp activity in human glioblastoma (U87, and its resistant variant U87-TxR with P-gp overexpression) and non-small cell lung carcinoma (NCI-H460, and its resistant variant NCI-H460/R with P-gp overexpression) cell lines. To that end, we used the accumulation assays of fluorescent P-gp substrates (rhodamine 123 and doxorubicin) that were analyzed by flow cytometry. An increase in the accumulation of the P-gp substrate corresponds to the level of P-gp activity suppression. Our results showed that simultaneous application of sclareol (20 μM and 50 μM) with either rhodamine 123 (5 μM) or doxorubicin (20 μM) significantly increased their accumulation in resistant cells (U87-TxR and NCI-H460/R) than in their corresponding sensitive cells (U87 and NCI-H460). The doxorubicin accumulation was also considerably increased in sensitive U87 cells implying that sclareol may interact with doxorubicin through other mechanisms in glioblastoma cells (not only by P-gp inhibition). Further investigations are envisioned to reveal the mechanisms behind sclareol and doxorubicin interaction in glioblastoma cells.",
publisher = "Belgrade: Faculty of Chemistry: Serbian Biochemical Society, 2021",
journal = "Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia",
title = "Sclareol, a natural compound, inhibits P-glycoprotein activity in cancer cells",
pages = "77",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5607"
}

Stepanović, A., Lupšić, E., Nikolić, A. M., Dragoj, M., Jovanović Stojanov, S., Novaković, M., Opsenica, I. M.,& Pešić, M.. (2021). Sclareol, a natural compound, inhibits P-glycoprotein activity in cancer cells. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
Belgrade: Faculty of Chemistry: Serbian Biochemical Society, 2021., 77.
https://hdl.handle.net/21.15107/rcub_ibiss_5607

Stepanović A, Lupšić E, Nikolić AM, Dragoj M, Jovanović Stojanov S, Novaković M, Opsenica IM, Pešić M. Sclareol, a natural compound, inhibits P-glycoprotein activity in cancer cells. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia. 2021;:77.
https://hdl.handle.net/21.15107/rcub_ibiss_5607 .

Stepanović, Ana, Lupšić, Ema, Nikolić, Andrea M., Dragoj, Miodrag, Jovanović Stojanov, Sofija, Novaković, Miroslav, Opsenica, Igor M., Pešić, Milica, "Sclareol, a natural compound, inhibits P-glycoprotein activity in cancer cells" in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia (2021):77,
https://hdl.handle.net/21.15107/rcub_ibiss_5607 .

TY  - JOUR
AU  - Krstić, Gordana
AU  - Stepanović, Ana
AU  - Jadranin, Milka
AU  - Pešić, Milica
AU  - Novaković, Miroslav
AU  - Aljančić, Ivana
AU  - Vajs, Vlatka
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4752
AB  - In the previous study fifteen jatrophane diterpenes were isolated from the Euphorbia nicaeensis latex. Fourteen of them have been shown to be potent P-glycoprotein (P-gp) inhibitor in two MDR cancer cells (NCI-H460/R and DLD1-TxR). The aim of this study was to determine whether and which jatro­phane diterpenes can be isolated from the root of the plant, and then to examine their inhibition power on P-glycoprotein of selected cancer cell lines (NCI-H460, DLD1, U87, NCI-H460/R, DLD1-TxR and U87-TxR). Two previously undes­cribed jatrophane diterpenes were isolated from the root of E. nicaeensis col­lected in Deliblato Sand (Serbia). The structures of the isolated compounds were determined using 1D and 2D NMR, as well as HRESIMS data. The results obtained by MTT assay showed different antitumor potential of these two jatrophanes. Compound 1 inhibited cell growth of non-small cell lung car­cinoma cell lines NCI-H460 and NCI-H460/R, as well as glioblastoma cell lines U87 and U87-TxR, while jatrophane 2 was almost completely inactive in the suppression of cancer cell growth in a given range of concentrations. The obtained results also showed that the isolated compounds have an inhibitory effect on P-glycoprotein, as well as that their inhibitory potential is similar.
PB  - Belgrade : Serbian Chemical Society
T2  - The Journal of the Serbian Chemical Society
T1  - Two new jatrophane diterpenes from the roots of Euphorbia nicaeensis
IS  - 12
VL  - 86
DO  - 10.2298/JSC210806085K
SP  - 1219
EP  - 1228
ER  - 

@article{
author = "Krstić, Gordana and Stepanović, Ana and Jadranin, Milka and Pešić, Milica and Novaković, Miroslav and Aljančić, Ivana and Vajs, Vlatka",
year = "2021",
abstract = "In the previous study fifteen jatrophane diterpenes were isolated from the Euphorbia nicaeensis latex. Fourteen of them have been shown to be potent P-glycoprotein (P-gp) inhibitor in two MDR cancer cells (NCI-H460/R and DLD1-TxR). The aim of this study was to determine whether and which jatro­phane diterpenes can be isolated from the root of the plant, and then to examine their inhibition power on P-glycoprotein of selected cancer cell lines (NCI-H460, DLD1, U87, NCI-H460/R, DLD1-TxR and U87-TxR). Two previously undes­cribed jatrophane diterpenes were isolated from the root of E. nicaeensis col­lected in Deliblato Sand (Serbia). The structures of the isolated compounds were determined using 1D and 2D NMR, as well as HRESIMS data. The results obtained by MTT assay showed different antitumor potential of these two jatrophanes. Compound 1 inhibited cell growth of non-small cell lung car­cinoma cell lines NCI-H460 and NCI-H460/R, as well as glioblastoma cell lines U87 and U87-TxR, while jatrophane 2 was almost completely inactive in the suppression of cancer cell growth in a given range of concentrations. The obtained results also showed that the isolated compounds have an inhibitory effect on P-glycoprotein, as well as that their inhibitory potential is similar.",
publisher = "Belgrade : Serbian Chemical Society",
journal = "The Journal of the Serbian Chemical Society",
title = "Two new jatrophane diterpenes from the roots of Euphorbia nicaeensis",
number = "12",
volume = "86",
doi = "10.2298/JSC210806085K",
pages = "1219-1228"
}

Krstić, G., Stepanović, A., Jadranin, M., Pešić, M., Novaković, M., Aljančić, I.,& Vajs, V.. (2021). Two new jatrophane diterpenes from the roots of Euphorbia nicaeensis. in The Journal of the Serbian Chemical Society
Belgrade : Serbian Chemical Society., 86(12), 1219-1228.
https://doi.org/10.2298/JSC210806085K

Krstić G, Stepanović A, Jadranin M, Pešić M, Novaković M, Aljančić I, Vajs V. Two new jatrophane diterpenes from the roots of Euphorbia nicaeensis. in The Journal of the Serbian Chemical Society. 2021;86(12):1219-1228.
doi:10.2298/JSC210806085K .

Krstić, Gordana, Stepanović, Ana, Jadranin, Milka, Pešić, Milica, Novaković, Miroslav, Aljančić, Ivana, Vajs, Vlatka, "Two new jatrophane diterpenes from the roots of Euphorbia nicaeensis" in The Journal of the Serbian Chemical Society, 86, no. 12 (2021):1219-1228,
https://doi.org/10.2298/JSC210806085K . .

TY  - CHAP
AU  - Dinić, Jelena
AU  - Novaković, Miroslav
AU  - Pešić, Milica
PY  - 2020
UR  - https://www.sciencedirect.com/science/article/pii/B9780128195413000098
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3843
AB  - Natural products represent a key source of novel drug leads and their essential value in anticancer research is being increasingly recognized. The presence, quantity, and structural characteristics of natural compounds within the same species could differ between regions as a result of environmental variations contributing to intraspecific chemodiversity. The Balkan Peninsula is a vital part of Europe’s biodiversity, with a considerable number of endemic species and with a broad ecosystem distribution. This region provides an unlimited supply of unique, structurally diverse compounds and offers vast potential for discovering and developing therapeutics for human benefit. This chapter gives an overview of anticancer compounds derived from natural sources of the Balkans and underlines the importance for the long-term conservation of biodiversity in this part of Europe.
PB  - Cambridge (Massachusetts, United States) : Academic Press - Elsevier
T2  - Biodiversity and Biomedicine: Our Future
T1  - Potential for cancer treatment: natural products from the Balkans
DO  - 10.1016/B978-0-12-819541-3.00009-8
SP  - 137
EP  - 159
ER  - 

@inbook{
author = "Dinić, Jelena and Novaković, Miroslav and Pešić, Milica",
year = "2020",
abstract = "Natural products represent a key source of novel drug leads and their essential value in anticancer research is being increasingly recognized. The presence, quantity, and structural characteristics of natural compounds within the same species could differ between regions as a result of environmental variations contributing to intraspecific chemodiversity. The Balkan Peninsula is a vital part of Europe’s biodiversity, with a considerable number of endemic species and with a broad ecosystem distribution. This region provides an unlimited supply of unique, structurally diverse compounds and offers vast potential for discovering and developing therapeutics for human benefit. This chapter gives an overview of anticancer compounds derived from natural sources of the Balkans and underlines the importance for the long-term conservation of biodiversity in this part of Europe.",
publisher = "Cambridge (Massachusetts, United States) : Academic Press - Elsevier",
journal = "Biodiversity and Biomedicine: Our Future",
booktitle = "Potential for cancer treatment: natural products from the Balkans",
doi = "10.1016/B978-0-12-819541-3.00009-8",
pages = "137-159"
}

Dinić, J., Novaković, M.,& Pešić, M.. (2020). Potential for cancer treatment: natural products from the Balkans. in Biodiversity and Biomedicine: Our Future
Cambridge (Massachusetts, United States) : Academic Press - Elsevier., 137-159.
https://doi.org/10.1016/B978-0-12-819541-3.00009-8

Dinić J, Novaković M, Pešić M. Potential for cancer treatment: natural products from the Balkans. in Biodiversity and Biomedicine: Our Future. 2020;:137-159.
doi:10.1016/B978-0-12-819541-3.00009-8 .

Dinić, Jelena, Novaković, Miroslav, Pešić, Milica, "Potential for cancer treatment: natural products from the Balkans" in Biodiversity and Biomedicine: Our Future (2020):137-159,
https://doi.org/10.1016/B978-0-12-819541-3.00009-8 . .

TY  - JOUR
AU  - Stanković, Jovana
AU  - Novaković, Miroslav
AU  - Tešević, Vele
AU  - Ćirić, Ana
AU  - Soković, Marina
AU  - Zdunić, Gordana
AU  - Dajić-Stevanović, Zora
AU  - Gođevac, Dejan
PY  - 2019
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3613
AB  - This study was performed to determine the main antibacterial com­po­unds of the essential oil (ЕО) of saltmarsh plant Artemisia santonicum (Aster­aceae). The combination of HPTLC and direct bioautography was used for the activity guided isolation of isogeranic acid as the main antibacterial constituent with remarkable antimicrobial activity, although it was the minor component of the EO, present only in 0.2 %, as calculated from GC/FID. Its structure was deter­mined by 1D- and 2D-NMR and GC–MS techniques. Antibacterial acti­vity of isogeranic acid against all tested bacteria was significantly higher than EO and even than both controls streptomycin and ampicillin. In further inves­tigation of antibiofilm and antiquorum sensing activity EO exhibited the best inhibition of the biofilm formation at 1/8 minimal inhibitory concentration (MIC) and iso­geranic acid at 1/2 MIC. Both EO and isogeranic acid possessed pyocyanin inhibitory activity showing the reduction of pigment at 60.6 and 62.8 %, res­pect­ively, at 1/2 MIC concentrations.
T2  - Journal of the Serbian Chemical Society
T1  - HPTLC-direct bioautography-guided isolation of isogeranic acid as the main antibacterial constituent of Artemisia santonicum essential oil
IS  - 12
VL  - 84
DO  - 10.2298/jsc190513106s
SP  - 1355
EP  - 1365
ER  - 

@article{
author = "Stanković, Jovana and Novaković, Miroslav and Tešević, Vele and Ćirić, Ana and Soković, Marina and Zdunić, Gordana and Dajić-Stevanović, Zora and Gođevac, Dejan",
year = "2019",
abstract = "This study was performed to determine the main antibacterial com­po­unds of the essential oil (ЕО) of saltmarsh plant Artemisia santonicum (Aster­aceae). The combination of HPTLC and direct bioautography was used for the activity guided isolation of isogeranic acid as the main antibacterial constituent with remarkable antimicrobial activity, although it was the minor component of the EO, present only in 0.2 %, as calculated from GC/FID. Its structure was deter­mined by 1D- and 2D-NMR and GC–MS techniques. Antibacterial acti­vity of isogeranic acid against all tested bacteria was significantly higher than EO and even than both controls streptomycin and ampicillin. In further inves­tigation of antibiofilm and antiquorum sensing activity EO exhibited the best inhibition of the biofilm formation at 1/8 minimal inhibitory concentration (MIC) and iso­geranic acid at 1/2 MIC. Both EO and isogeranic acid possessed pyocyanin inhibitory activity showing the reduction of pigment at 60.6 and 62.8 %, res­pect­ively, at 1/2 MIC concentrations.",
journal = "Journal of the Serbian Chemical Society",
title = "HPTLC-direct bioautography-guided isolation of isogeranic acid as the main antibacterial constituent of Artemisia santonicum essential oil",
number = "12",
volume = "84",
doi = "10.2298/jsc190513106s",
pages = "1355-1365"
}

Stanković, J., Novaković, M., Tešević, V., Ćirić, A., Soković, M., Zdunić, G., Dajić-Stevanović, Z.,& Gođevac, D.. (2019). HPTLC-direct bioautography-guided isolation of isogeranic acid as the main antibacterial constituent of Artemisia santonicum essential oil. in Journal of the Serbian Chemical Society, 84(12), 1355-1365.
https://doi.org/10.2298/jsc190513106s

Stanković J, Novaković M, Tešević V, Ćirić A, Soković M, Zdunić G, Dajić-Stevanović Z, Gođevac D. HPTLC-direct bioautography-guided isolation of isogeranic acid as the main antibacterial constituent of Artemisia santonicum essential oil. in Journal of the Serbian Chemical Society. 2019;84(12):1355-1365.
doi:10.2298/jsc190513106s .

Stanković, Jovana, Novaković, Miroslav, Tešević, Vele, Ćirić, Ana, Soković, Marina, Zdunić, Gordana, Dajić-Stevanović, Zora, Gođevac, Dejan, "HPTLC-direct bioautography-guided isolation of isogeranic acid as the main antibacterial constituent of Artemisia santonicum essential oil" in Journal of the Serbian Chemical Society, 84, no. 12 (2019):1355-1365,
https://doi.org/10.2298/jsc190513106s . .

TY  - JOUR
AU  - Stanković, Jovana
AU  - Gođevac, Dejan
AU  - Tešević, Vele
AU  - Dajić-Stevanović, Zora
AU  - Ćirić, Ana
AU  - Soković, Marina
AU  - Novaković, Miroslav
PY  - 2019
UR  - http://pubs.acs.org/doi/10.1021/acs.jnatprod.8b00970
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3397
AB  - A new flavonoid glucoside derivative, patuletin 3 -O-(2- O-feruloyl)-β-d-glucuronopyranosyl-(1→2)-β-d-glucopyranoside, named atriplexin IV (1), and three new triterpenoid saponin derivatives, two sulfonylated, β-d-glucopyranosyl-3 -O-(2- O-sulfo-β-d-galactopyranosyl)-(1→2)-α-l-arabinopyranoside-30-alolean-12-en-28-oate (2), named atriplexogenin I, β-d-glucopyranosyl-3- O-(2- O-sulfo-β-d-galactopyranosyl)-(1→2)-α-l-arabinopyranoside)-30-hydroxyolean-12-en-28-oate (3), named atriplexogenin II, and β-d-glucopyranosyl-3 -O-(β-d-glucopyranosyl-(1→2)-β-d-galactopyranosyl-(1→2)-α-l-arabinopyranoside)-30-alolean-12-en-28-oate (4), named atriplexogenin III, were isolated by silica gel column and semipreparative HPLC chromatography from the n-butanol extract of the salt marsh plant Atriplex tatarica. In addition, two known secondary metabolites, patuletin3 -O-β-d-apiofuranosyl-(1‴→2″)-β-d-glucopyranoside (5) and patuletin 3 -O-5‴- O-feruloyl-β-d-apiofuranosyl-(1‴→2″)-β-d-glucopyranoside (6), were isolated for the first time from A. tatarica. The structures of the isolated compounds were elucidated by 1D and 2D NMR, HRESIMS, IR, and UV data. Antibacterial activity by the microdilution method and antibiofilm activity against P. aeruginosa were assessed. Compound 5 possesses significant antibacterial activity, while the most potent antibiofilm agent is compound 2.
PB  - American Chemical Society and American Society of Pharmacognosy
T2  - Journal of Natural Products
T1  - Antibacterial and Antibiofilm Activity of Flavonoid and Saponin Derivatives from Atriplex tatarica against Pseudomonas aeruginosa.
IS  - 6
VL  - 82
DO  - 10.1021/acs.jnatprod.8b00970
SP  - 1487
EP  - 1495
ER  - 

@article{
author = "Stanković, Jovana and Gođevac, Dejan and Tešević, Vele and Dajić-Stevanović, Zora and Ćirić, Ana and Soković, Marina and Novaković, Miroslav",
year = "2019",
abstract = "A new flavonoid glucoside derivative, patuletin 3 -O-(2- O-feruloyl)-β-d-glucuronopyranosyl-(1→2)-β-d-glucopyranoside, named atriplexin IV (1), and three new triterpenoid saponin derivatives, two sulfonylated, β-d-glucopyranosyl-3 -O-(2- O-sulfo-β-d-galactopyranosyl)-(1→2)-α-l-arabinopyranoside-30-alolean-12-en-28-oate (2), named atriplexogenin I, β-d-glucopyranosyl-3- O-(2- O-sulfo-β-d-galactopyranosyl)-(1→2)-α-l-arabinopyranoside)-30-hydroxyolean-12-en-28-oate (3), named atriplexogenin II, and β-d-glucopyranosyl-3 -O-(β-d-glucopyranosyl-(1→2)-β-d-galactopyranosyl-(1→2)-α-l-arabinopyranoside)-30-alolean-12-en-28-oate (4), named atriplexogenin III, were isolated by silica gel column and semipreparative HPLC chromatography from the n-butanol extract of the salt marsh plant Atriplex tatarica. In addition, two known secondary metabolites, patuletin3 -O-β-d-apiofuranosyl-(1‴→2″)-β-d-glucopyranoside (5) and patuletin 3 -O-5‴- O-feruloyl-β-d-apiofuranosyl-(1‴→2″)-β-d-glucopyranoside (6), were isolated for the first time from A. tatarica. The structures of the isolated compounds were elucidated by 1D and 2D NMR, HRESIMS, IR, and UV data. Antibacterial activity by the microdilution method and antibiofilm activity against P. aeruginosa were assessed. Compound 5 possesses significant antibacterial activity, while the most potent antibiofilm agent is compound 2.",
publisher = "American Chemical Society and American Society of Pharmacognosy",
journal = "Journal of Natural Products",
title = "Antibacterial and Antibiofilm Activity of Flavonoid and Saponin Derivatives from Atriplex tatarica against Pseudomonas aeruginosa.",
number = "6",
volume = "82",
doi = "10.1021/acs.jnatprod.8b00970",
pages = "1487-1495"
}

Stanković, J., Gođevac, D., Tešević, V., Dajić-Stevanović, Z., Ćirić, A., Soković, M.,& Novaković, M.. (2019). Antibacterial and Antibiofilm Activity of Flavonoid and Saponin Derivatives from Atriplex tatarica against Pseudomonas aeruginosa.. in Journal of Natural Products
American Chemical Society and American Society of Pharmacognosy., 82(6), 1487-1495.
https://doi.org/10.1021/acs.jnatprod.8b00970

Stanković J, Gođevac D, Tešević V, Dajić-Stevanović Z, Ćirić A, Soković M, Novaković M. Antibacterial and Antibiofilm Activity of Flavonoid and Saponin Derivatives from Atriplex tatarica against Pseudomonas aeruginosa.. in Journal of Natural Products. 2019;82(6):1487-1495.
doi:10.1021/acs.jnatprod.8b00970 .

Stanković, Jovana, Gođevac, Dejan, Tešević, Vele, Dajić-Stevanović, Zora, Ćirić, Ana, Soković, Marina, Novaković, Miroslav, "Antibacterial and Antibiofilm Activity of Flavonoid and Saponin Derivatives from Atriplex tatarica against Pseudomonas aeruginosa." in Journal of Natural Products, 82, no. 6 (2019):1487-1495,
https://doi.org/10.1021/acs.jnatprod.8b00970 . .

TY  - JOUR
AU  - Vidaković, Vera
AU  - Marković, Milena
AU  - Novaković, Miroslav
AU  - Jadranin, Milka
AU  - Popović, Zorica
AU  - Matić, Rada
AU  - Tešević, Vele
AU  - Bojović, Srđan
PY  - 2018
UR  - http://www.degruyter.com/view/j/hfsg.ahead-of-print/hf-2018-0019/hf-2018-0019.xml
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3113
AB  - The reliability of diarylheptanoids as chemotaxonomic markers at inter- and intraspecific levels has been investigated. Six diarylheptanoids were quantified in bark ethanol extracts of four Alnus spp. populations by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The populations described here as locus classicus Alnus glutinosa (I) and locus classicus Alnus incana (III) are clearly differentiated. Compared to population I, individuals in population III have higher extract yields and hirsutanonol-5- O - β -D-glucopyranoside content and lower contents of hirsutanonol, rubranoside A and oregonin. Individuals from neighboring populations of A. glutinosa (II) and A. incana (IV) share similar contents of hirsutanonol. All the studied populations exhibit a high intrapopulation variability of the selected diarylheptanoids; they have a heterogeneous chemotype and they partially overlap. The geographical proximity of populations II and IV increases their chemical similarity. Principal component analysis (PCA) clearly shows that the biggest dispersion of individuals lies within population IV. The reason for its heterogeneity might be its physical proximity to population II, i.e. the appearance of hybrids. Also, geometric morphometrics of leaves was performed as a screening criterion for spontaneous hybrids.
T2  - Holzforschung
T1  - Inter- and intraspecific variability of selected diarylheptanoid compounds and leaf morphometric traits in Alnus glutinosa and Alnus incana
IS  - 12
VL  - 72
VL  - 12
DO  - 10.1515/hf-2018-0019
SP  - 1031
EP  - 1041
ER  - 

@article{
author = "Vidaković, Vera and Marković, Milena and Novaković, Miroslav and Jadranin, Milka and Popović, Zorica and Matić, Rada and Tešević, Vele and Bojović, Srđan",
year = "2018",
abstract = "The reliability of diarylheptanoids as chemotaxonomic markers at inter- and intraspecific levels has been investigated. Six diarylheptanoids were quantified in bark ethanol extracts of four Alnus spp. populations by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The populations described here as locus classicus Alnus glutinosa (I) and locus classicus Alnus incana (III) are clearly differentiated. Compared to population I, individuals in population III have higher extract yields and hirsutanonol-5- O - β -D-glucopyranoside content and lower contents of hirsutanonol, rubranoside A and oregonin. Individuals from neighboring populations of A. glutinosa (II) and A. incana (IV) share similar contents of hirsutanonol. All the studied populations exhibit a high intrapopulation variability of the selected diarylheptanoids; they have a heterogeneous chemotype and they partially overlap. The geographical proximity of populations II and IV increases their chemical similarity. Principal component analysis (PCA) clearly shows that the biggest dispersion of individuals lies within population IV. The reason for its heterogeneity might be its physical proximity to population II, i.e. the appearance of hybrids. Also, geometric morphometrics of leaves was performed as a screening criterion for spontaneous hybrids.",
journal = "Holzforschung",
title = "Inter- and intraspecific variability of selected diarylheptanoid compounds and leaf morphometric traits in Alnus glutinosa and Alnus incana",
number = "12",
volume = "72, 12",
doi = "10.1515/hf-2018-0019",
pages = "1031-1041"
}

Vidaković, V., Marković, M., Novaković, M., Jadranin, M., Popović, Z., Matić, R., Tešević, V.,& Bojović, S.. (2018). Inter- and intraspecific variability of selected diarylheptanoid compounds and leaf morphometric traits in Alnus glutinosa and Alnus incana. in Holzforschung, 72(12), 1031-1041.
https://doi.org/10.1515/hf-2018-0019

Vidaković V, Marković M, Novaković M, Jadranin M, Popović Z, Matić R, Tešević V, Bojović S. Inter- and intraspecific variability of selected diarylheptanoid compounds and leaf morphometric traits in Alnus glutinosa and Alnus incana. in Holzforschung. 2018;72(12):1031-1041.
doi:10.1515/hf-2018-0019 .

Vidaković, Vera, Marković, Milena, Novaković, Miroslav, Jadranin, Milka, Popović, Zorica, Matić, Rada, Tešević, Vele, Bojović, Srđan, "Inter- and intraspecific variability of selected diarylheptanoid compounds and leaf morphometric traits in Alnus glutinosa and Alnus incana" in Holzforschung, 72, no. 12 (2018):1031-1041,
https://doi.org/10.1515/hf-2018-0019 . .

TY  - JOUR
AU  - Vidaković, Vera
AU  - Novaković, Miroslav
AU  - Popović, Zorica
AU  - Janković, Milan
AU  - Matić, Rada
AU  - Tešević, Vele
AU  - Bojović, Srđan
PY  - 2018
UR  - http://www.degruyter.com/view/j/hfsg.2018.72.issue-1/hf-2017-0074/hf-2017-0074.xml
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3112
AB  - Diarylheptanoids are a group of secondary metabolites widely distributed in the Betulaceae family and characteristic for Alnus species. In this study, the chemotaxonomic power of diarylheptanoids, such as hirsutanonol-5-O-β-d-glucopyranoside, rubranoside A, oregonin, platyphylloside, alnuside A and hirsutanonol, has been investigated in combination with principal component analysis (PCA) for differentiation of Alnus species. Concentrations of six diarylheptanoids in the bark extracts of two natural populations of Alnus glutinosa (black alder) and Alnus incana (gray alder) were determined by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). PCA clearly shows the separation of three groups. Populations I (A. glutinosa) and II (A. incana) both consisted of individuals of the corresponding species. Four individuals from both sampled populations formed a separate group (population III), which possibly represents a hybrid group. Accordingly, diarylheptanoids may serve in combination with PCA as chemotaxonomic markers at the species level, which may also reveal hybrid species.
T2  - Holzforschung
T1  - Significance of diarylheptanoids for chemotaxonomical distinguishing between Alnus glutinosa and Alnus incana
IS  - 1
VL  - 72
DO  - 10.1515/hf-2017-0074
SP  - 9
EP  - 16
ER  - 

@article{
author = "Vidaković, Vera and Novaković, Miroslav and Popović, Zorica and Janković, Milan and Matić, Rada and Tešević, Vele and Bojović, Srđan",
year = "2018",
abstract = "Diarylheptanoids are a group of secondary metabolites widely distributed in the Betulaceae family and characteristic for Alnus species. In this study, the chemotaxonomic power of diarylheptanoids, such as hirsutanonol-5-O-β-d-glucopyranoside, rubranoside A, oregonin, platyphylloside, alnuside A and hirsutanonol, has been investigated in combination with principal component analysis (PCA) for differentiation of Alnus species. Concentrations of six diarylheptanoids in the bark extracts of two natural populations of Alnus glutinosa (black alder) and Alnus incana (gray alder) were determined by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). PCA clearly shows the separation of three groups. Populations I (A. glutinosa) and II (A. incana) both consisted of individuals of the corresponding species. Four individuals from both sampled populations formed a separate group (population III), which possibly represents a hybrid group. Accordingly, diarylheptanoids may serve in combination with PCA as chemotaxonomic markers at the species level, which may also reveal hybrid species.",
journal = "Holzforschung",
title = "Significance of diarylheptanoids for chemotaxonomical distinguishing between Alnus glutinosa and Alnus incana",
number = "1",
volume = "72",
doi = "10.1515/hf-2017-0074",
pages = "9-16"
}

Vidaković, V., Novaković, M., Popović, Z., Janković, M., Matić, R., Tešević, V.,& Bojović, S.. (2018). Significance of diarylheptanoids for chemotaxonomical distinguishing between Alnus glutinosa and Alnus incana. in Holzforschung, 72(1), 9-16.
https://doi.org/10.1515/hf-2017-0074

Vidaković V, Novaković M, Popović Z, Janković M, Matić R, Tešević V, Bojović S. Significance of diarylheptanoids for chemotaxonomical distinguishing between Alnus glutinosa and Alnus incana. in Holzforschung. 2018;72(1):9-16.
doi:10.1515/hf-2017-0074 .

Vidaković, Vera, Novaković, Miroslav, Popović, Zorica, Janković, Milan, Matić, Rada, Tešević, Vele, Bojović, Srđan, "Significance of diarylheptanoids for chemotaxonomical distinguishing between Alnus glutinosa and Alnus incana" in Holzforschung, 72, no. 1 (2018):9-16,
https://doi.org/10.1515/hf-2017-0074 . .

TY  - JOUR
AU  - Ilić-Tomić, Tatjana
AU  - Soković, Marina
AU  - Vojnović, Sandra
AU  - Ćirić, Ana
AU  - Veljić, Milan
AU  - Nikodinović-Runić, Jasmina
AU  - Novaković, Miroslav
PY  - 2017
UR  - http://www.thieme-connect.de/DOI/DOI?10.1055/s-0042-107674
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2686
AB  - Diarylheptanoids from the barks of Alnus viridis ssp. viridis (green alder) and Alnus glutinosa (black alder) were explored for anti-quorum sensing activity. Chemicals with anti-quorum sensing activity have recently been examined for antimicrobial applications. The anti-quorum sensing activity of the selected diarylheptanoids was determined using two biosensors, namely Pseudomonas aeruginosa PAO1 and Chromobacterium violaceum CV026. Although all of the investigated compounds negatively influenced the motility of P. aeruginosa PAO1, four were able to inhibit biofilm formation of this human opportunistic pathogen for 40–70?%. Three of the diarylheptanoids (3, 4, and 5) negatively influenced the biosynthesis of pyocyanin, which is under the control of quorum sensing. Platyphyllenone (7) and hirsutenone (5) were able to inhibit the biosynthesis of violacein in C. violaceum CV026, with 5 being able to inhibit the synthesis of both biopigments. Only one of the tested diarylheptanoids (1) was shown to significantly decrease the production of acyl homoserine lactones (AHL) in P. aeruginosa PAO1, more specifically, production of the long chain N-(3-oxododecanoyl)-l-HSL. On the other side, four diarylheptanoids (2–5) significantly reduced the synthesis of 2-alkyl-4-quinolones, part of the P. aeruginosa quinolone-mediated signaling system. To properly assess therapeutic potential of these compounds, their in vitro antiproliferative effect on normal human lung fibroblasts was determined, with doses affecting cell proliferation between 10 and 100 µg/mL. This study confirms that the barks of green and black alders are rich source of phytochemicals with a wide range of biological activities that could further be exploited as natural agents against bacterial contaminations and infections.
T2  - Planta Medica
T1  - Diarylheptanoids from Alnus viridis ssp. viridis and Alnus glutinosa: Modulation of Quorum Sensing Activity in Pseudomonas aeruginosa
IS  - 01/02
VL  - 83
DO  - 10.1055/s-0042-107674
SP  - 117
EP  - 125
ER  - 

@article{
author = "Ilić-Tomić, Tatjana and Soković, Marina and Vojnović, Sandra and Ćirić, Ana and Veljić, Milan and Nikodinović-Runić, Jasmina and Novaković, Miroslav",
year = "2017",
abstract = "Diarylheptanoids from the barks of Alnus viridis ssp. viridis (green alder) and Alnus glutinosa (black alder) were explored for anti-quorum sensing activity. Chemicals with anti-quorum sensing activity have recently been examined for antimicrobial applications. The anti-quorum sensing activity of the selected diarylheptanoids was determined using two biosensors, namely Pseudomonas aeruginosa PAO1 and Chromobacterium violaceum CV026. Although all of the investigated compounds negatively influenced the motility of P. aeruginosa PAO1, four were able to inhibit biofilm formation of this human opportunistic pathogen for 40–70?%. Three of the diarylheptanoids (3, 4, and 5) negatively influenced the biosynthesis of pyocyanin, which is under the control of quorum sensing. Platyphyllenone (7) and hirsutenone (5) were able to inhibit the biosynthesis of violacein in C. violaceum CV026, with 5 being able to inhibit the synthesis of both biopigments. Only one of the tested diarylheptanoids (1) was shown to significantly decrease the production of acyl homoserine lactones (AHL) in P. aeruginosa PAO1, more specifically, production of the long chain N-(3-oxododecanoyl)-l-HSL. On the other side, four diarylheptanoids (2–5) significantly reduced the synthesis of 2-alkyl-4-quinolones, part of the P. aeruginosa quinolone-mediated signaling system. To properly assess therapeutic potential of these compounds, their in vitro antiproliferative effect on normal human lung fibroblasts was determined, with doses affecting cell proliferation between 10 and 100 µg/mL. This study confirms that the barks of green and black alders are rich source of phytochemicals with a wide range of biological activities that could further be exploited as natural agents against bacterial contaminations and infections.",
journal = "Planta Medica",
title = "Diarylheptanoids from Alnus viridis ssp. viridis and Alnus glutinosa: Modulation of Quorum Sensing Activity in Pseudomonas aeruginosa",
number = "01/02",
volume = "83",
doi = "10.1055/s-0042-107674",
pages = "117-125"
}

Ilić-Tomić, T., Soković, M., Vojnović, S., Ćirić, A., Veljić, M., Nikodinović-Runić, J.,& Novaković, M.. (2017). Diarylheptanoids from Alnus viridis ssp. viridis and Alnus glutinosa: Modulation of Quorum Sensing Activity in Pseudomonas aeruginosa. in Planta Medica, 83(01/02), 117-125.
https://doi.org/10.1055/s-0042-107674

Ilić-Tomić T, Soković M, Vojnović S, Ćirić A, Veljić M, Nikodinović-Runić J, Novaković M. Diarylheptanoids from Alnus viridis ssp. viridis and Alnus glutinosa: Modulation of Quorum Sensing Activity in Pseudomonas aeruginosa. in Planta Medica. 2017;83(01/02):117-125.
doi:10.1055/s-0042-107674 .

Ilić-Tomić, Tatjana, Soković, Marina, Vojnović, Sandra, Ćirić, Ana, Veljić, Milan, Nikodinović-Runić, Jasmina, Novaković, Miroslav, "Diarylheptanoids from Alnus viridis ssp. viridis and Alnus glutinosa: Modulation of Quorum Sensing Activity in Pseudomonas aeruginosa" in Planta Medica, 83, no. 01/02 (2017):117-125,
https://doi.org/10.1055/s-0042-107674 . .

TY  - JOUR
AU  - Novaković, Miroslav
AU  - Nikodinović-Runić, Jasmina
AU  - Veselinović, Jovana
AU  - Ilić-Tomić, Tatjana
AU  - Vidaković, Vera
AU  - Tešević, Vele
AU  - Milosavljević, Slobodan
PY  - 2017
UR  - http://pubs.acs.org/doi/abs/10.1021/acs.jnatprod.6b00805
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2765
AB  - Seven derivatives of pentacyclic triterpene acids (1-7) were isolated from the bark of Alnus viridis ssp. viridis using a combination of column chromatography and semipreparative HPLC. Compounds 1-3, 6, and 7 were determined to be new after spectroscopic data interpretation and were assigned as 27-hydroxyalphitolic acid derivatives (1-3), a 27-hydroxybetulinic acid derivative (6), and a 3-epi-maslinic acid derivative (7), respectively. Pentacyclic triterpenoids with a C-27 hydroxymethyl group have been found in species of the genus Alnus for the first time. These compounds were subjected to cytotoxicity testing against a number of cancer cell lines. Also, selected pentacyclic triterpenoids were selected as potential inhibitors of topoisomerases I and IIα for an in silico investigation.
T2  - Journal of Natural Products
T1  - Bioactive Pentacyclic Triterpene Ester Derivatives from Alnus viridis ssp. viridis Bark
IS  - 5
VL  - 80
DO  - 10.1021/acs.jnatprod.6b00805
SP  - 1255
EP  - 1263
ER  - 

@article{
author = "Novaković, Miroslav and Nikodinović-Runić, Jasmina and Veselinović, Jovana and Ilić-Tomić, Tatjana and Vidaković, Vera and Tešević, Vele and Milosavljević, Slobodan",
year = "2017",
abstract = "Seven derivatives of pentacyclic triterpene acids (1-7) were isolated from the bark of Alnus viridis ssp. viridis using a combination of column chromatography and semipreparative HPLC. Compounds 1-3, 6, and 7 were determined to be new after spectroscopic data interpretation and were assigned as 27-hydroxyalphitolic acid derivatives (1-3), a 27-hydroxybetulinic acid derivative (6), and a 3-epi-maslinic acid derivative (7), respectively. Pentacyclic triterpenoids with a C-27 hydroxymethyl group have been found in species of the genus Alnus for the first time. These compounds were subjected to cytotoxicity testing against a number of cancer cell lines. Also, selected pentacyclic triterpenoids were selected as potential inhibitors of topoisomerases I and IIα for an in silico investigation.",
journal = "Journal of Natural Products",
title = "Bioactive Pentacyclic Triterpene Ester Derivatives from Alnus viridis ssp. viridis Bark",
number = "5",
volume = "80",
doi = "10.1021/acs.jnatprod.6b00805",
pages = "1255-1263"
}

Novaković, M., Nikodinović-Runić, J., Veselinović, J., Ilić-Tomić, T., Vidaković, V., Tešević, V.,& Milosavljević, S.. (2017). Bioactive Pentacyclic Triterpene Ester Derivatives from Alnus viridis ssp. viridis Bark. in Journal of Natural Products, 80(5), 1255-1263.
https://doi.org/10.1021/acs.jnatprod.6b00805

Novaković M, Nikodinović-Runić J, Veselinović J, Ilić-Tomić T, Vidaković V, Tešević V, Milosavljević S. Bioactive Pentacyclic Triterpene Ester Derivatives from Alnus viridis ssp. viridis Bark. in Journal of Natural Products. 2017;80(5):1255-1263.
doi:10.1021/acs.jnatprod.6b00805 .

Novaković, Miroslav, Nikodinović-Runić, Jasmina, Veselinović, Jovana, Ilić-Tomić, Tatjana, Vidaković, Vera, Tešević, Vele, Milosavljević, Slobodan, "Bioactive Pentacyclic Triterpene Ester Derivatives from Alnus viridis ssp. viridis Bark" in Journal of Natural Products, 80, no. 5 (2017):1255-1263,
https://doi.org/10.1021/acs.jnatprod.6b00805 . .

TY  - JOUR
AU  - Bukvički, Danka R.
AU  - Ćirić, Ana
AU  - Soković, Marina
AU  - Vannini, Lucia
AU  - Nissen, Lorenzo
AU  - Novaković, Miroslav
AU  - Vujisić, Ljubodrag
AU  - Asakawa, Yoshinori
AU  - Marin, Petar D.
PY  - 2016
UR  - http://www.naturalproduct.us/
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2754
AB  - The chemical composition, antimicrobial and antiquorum sensing activity of the essential oil of Micromeria thymifolia (Scop.) Fritsch were investigated. Limonene, piperitone epoxide and piperitenone epoxide were found as the main constituents using a gas chromatography-mass spectrometry technique. In vitro antimicrobial activity of the oil was tested against six bacterial and seven fungal strains and high antimicrobial potential was noticed. Minimum inhibitory concentration varied from 0.031 mg/mL to 0.5 mg/mL for bacterial and 0.062 mg/mL to 0.5 mg/mL for fungal strains. The antiquorum properties of the essential oil were evaluated on Pseudomonas aeruginosa PAO1. The oil was tested at subMIC concentrations for anti-quorum sensing activity. The analyses on quorum-sensing functions have been carried out by evaluating twitching and swarming of bacterial cultures and the total amount of pyocyanin production produced by P. aeruginosa. This study showed that M. thymifolia essential oil exhibited antiquorum sensing activity and may be used as an antipathogenic drug.
T2  - Natural Product Communications
T1  - Micromeria thymifolia essential oil suppresses quorum-sensing signaling in pseudomonas aeruginosa
IS  - 12
VL  - 11
DO  - 10.1177/1934578x1601101232
SP  - 1903
EP  - 1906
ER  - 

@article{
author = "Bukvički, Danka R. and Ćirić, Ana and Soković, Marina and Vannini, Lucia and Nissen, Lorenzo and Novaković, Miroslav and Vujisić, Ljubodrag and Asakawa, Yoshinori and Marin, Petar D.",
year = "2016",
abstract = "The chemical composition, antimicrobial and antiquorum sensing activity of the essential oil of Micromeria thymifolia (Scop.) Fritsch were investigated. Limonene, piperitone epoxide and piperitenone epoxide were found as the main constituents using a gas chromatography-mass spectrometry technique. In vitro antimicrobial activity of the oil was tested against six bacterial and seven fungal strains and high antimicrobial potential was noticed. Minimum inhibitory concentration varied from 0.031 mg/mL to 0.5 mg/mL for bacterial and 0.062 mg/mL to 0.5 mg/mL for fungal strains. The antiquorum properties of the essential oil were evaluated on Pseudomonas aeruginosa PAO1. The oil was tested at subMIC concentrations for anti-quorum sensing activity. The analyses on quorum-sensing functions have been carried out by evaluating twitching and swarming of bacterial cultures and the total amount of pyocyanin production produced by P. aeruginosa. This study showed that M. thymifolia essential oil exhibited antiquorum sensing activity and may be used as an antipathogenic drug.",
journal = "Natural Product Communications",
title = "Micromeria thymifolia essential oil suppresses quorum-sensing signaling in pseudomonas aeruginosa",
number = "12",
volume = "11",
doi = "10.1177/1934578x1601101232",
pages = "1903-1906"
}

Bukvički, D. R., Ćirić, A., Soković, M., Vannini, L., Nissen, L., Novaković, M., Vujisić, L., Asakawa, Y.,& Marin, P. D.. (2016). Micromeria thymifolia essential oil suppresses quorum-sensing signaling in pseudomonas aeruginosa. in Natural Product Communications, 11(12), 1903-1906.
https://doi.org/10.1177/1934578x1601101232

Bukvički DR, Ćirić A, Soković M, Vannini L, Nissen L, Novaković M, Vujisić L, Asakawa Y, Marin PD. Micromeria thymifolia essential oil suppresses quorum-sensing signaling in pseudomonas aeruginosa. in Natural Product Communications. 2016;11(12):1903-1906.
doi:10.1177/1934578x1601101232 .

Bukvički, Danka R., Ćirić, Ana, Soković, Marina, Vannini, Lucia, Nissen, Lorenzo, Novaković, Miroslav, Vujisić, Ljubodrag, Asakawa, Yoshinori, Marin, Petar D., "Micromeria thymifolia essential oil suppresses quorum-sensing signaling in pseudomonas aeruginosa" in Natural Product Communications, 11, no. 12 (2016):1903-1906,
https://doi.org/10.1177/1934578x1601101232 . .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Novaković, Miroslav
AU  - Podolski-Renić, Ana
AU  - Vajs, Vlatka
AU  - Tešević, Vele
AU  - Isaković, Aleksandra
AU  - Pešić, Milica
PY  - 2016
UR  - https://www.sciencedirect.com/science/article/pii/S0009279716300552
UR  - https://radar.ibiss.bg.ac.rs/123456789/3876
AB  - Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 3' and 3″-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 3' and 3″-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells.
PB  - Shannon : Elsevier
T2  - Chemico-Biological Interactions
T1  - Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells
VL  - 249
DO  - 10.1016/j.cbi.2016.02.019
SP  - 36
EP  - 45
ER  - 

@article{
author = "Dinić, Jelena and Novaković, Miroslav and Podolski-Renić, Ana and Vajs, Vlatka and Tešević, Vele and Isaković, Aleksandra and Pešić, Milica",
year = "2016",
abstract = "Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 3' and 3″-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 3' and 3″-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells.",
publisher = "Shannon : Elsevier",
journal = "Chemico-Biological Interactions",
title = "Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells",
volume = "249",
doi = "10.1016/j.cbi.2016.02.019",
pages = "36-45"
}

Dinić, J., Novaković, M., Podolski-Renić, A., Vajs, V., Tešević, V., Isaković, A.,& Pešić, M.. (2016). Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells. in Chemico-Biological Interactions
Shannon : Elsevier., 249, 36-45.
https://doi.org/10.1016/j.cbi.2016.02.019

Dinić J, Novaković M, Podolski-Renić A, Vajs V, Tešević V, Isaković A, Pešić M. Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells. in Chemico-Biological Interactions. 2016;249:36-45.
doi:10.1016/j.cbi.2016.02.019 .

Dinić, Jelena, Novaković, Miroslav, Podolski-Renić, Ana, Vajs, Vlatka, Tešević, Vele, Isaković, Aleksandra, Pešić, Milica, "Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells" in Chemico-Biological Interactions, 249 (2016):36-45,
https://doi.org/10.1016/j.cbi.2016.02.019 . .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Novaković, Miroslav
AU  - Podolski-Renić, Ana
AU  - Vajs, Vlatka
AU  - Tešević, Vele
AU  - Isaković, Aleksandra
AU  - Pešić, Milica
PY  - 2016
UR  - http://www.scopus.com/inward/record.url?eid=2-s2.0-84960351174&partnerID=tZOtx3y1
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2535
AB  - Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 3' and 3″-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 3' and 3″-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells.
T2  - Chemico-Biological Interactions
T1  - Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells.
VL  - 249
DO  - 10.1016/j.cbi.2016.02.019
SP  - 36
EP  - 45
ER  - 

@article{
author = "Dinić, Jelena and Novaković, Miroslav and Podolski-Renić, Ana and Vajs, Vlatka and Tešević, Vele and Isaković, Aleksandra and Pešić, Milica",
year = "2016",
abstract = "Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 3' and 3″-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 3' and 3″-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells.",
journal = "Chemico-Biological Interactions",
title = "Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells.",
volume = "249",
doi = "10.1016/j.cbi.2016.02.019",
pages = "36-45"
}

Dinić, J., Novaković, M., Podolski-Renić, A., Vajs, V., Tešević, V., Isaković, A.,& Pešić, M.. (2016). Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells.. in Chemico-Biological Interactions, 249, 36-45.
https://doi.org/10.1016/j.cbi.2016.02.019

Dinić J, Novaković M, Podolski-Renić A, Vajs V, Tešević V, Isaković A, Pešić M. Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells.. in Chemico-Biological Interactions. 2016;249:36-45.
doi:10.1016/j.cbi.2016.02.019 .

Dinić, Jelena, Novaković, Miroslav, Podolski-Renić, Ana, Vajs, Vlatka, Tešević, Vele, Isaković, Aleksandra, Pešić, Milica, "Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells." in Chemico-Biological Interactions, 249 (2016):36-45,
https://doi.org/10.1016/j.cbi.2016.02.019 . .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Ranđelović, Teodora
AU  - Stanković, Tijana
AU  - Dragoj, Miodrag
AU  - Isaković, Aleksandra
AU  - Novaković, Miroslav
AU  - Pešić, Milica
PY  - 2015
UR  - https://www.sciencedirect.com/science/article/abs/pii/S0367326X1530040X
UR  - https://radar.ibiss.bg.ac.rs/123456789/3865
AB  - Medicinal plants are recognized from ancient times as a source of diverse therapeutic agents and many of them are used as dietary supplements. Comprehensive approaches are needed that would identify bioactive components with evident activity against specific indications and provide a better link between science (ethno-botany, chemistry, biology and pharmacology) and market. Recently, the bark of black alder (Alnus glutinosa) appeared at market in the form of food supplement for treatment of different skin conditions. This study aimed to evaluate protective effects of two diarylheptanoids isolated from the bark of black alder: platyphylloside, 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-β-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-β-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2) towards doxorubicin damaging activity. To that end, we employed HaCaT cells, non-cancerous human keratinocytes commonly used for skin regenerative studies. Diarylheptanoids significantly antagonized the effects of doxorubicin by lowering the sensitivity of HaCaT cells to this drug. Compound 2 prevented doxorubicin-induced cell death by activating autophagy. Both 1 and 2 protected HaCaT cells against doxorubicin-induced DNA damage. They significantly promoted migration and affected F-actin distribution. These results indicate that chemo-protective effects of diarylheptanoids may occur at multiple subcellular levels. Therefore, diarylheptanoids 1 and 2 could be considered as protective agents for non-cancerous dividing cells during chemotherapy.
PB  - Elsevier
T2  - Fitoterapia
T1  - Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes
VL  - 105
DO  - 10.1016/j.fitote.2015.07.003
SP  - 169
EP  - 176
ER  - 

@article{
author = "Dinić, Jelena and Ranđelović, Teodora and Stanković, Tijana and Dragoj, Miodrag and Isaković, Aleksandra and Novaković, Miroslav and Pešić, Milica",
year = "2015",
abstract = "Medicinal plants are recognized from ancient times as a source of diverse therapeutic agents and many of them are used as dietary supplements. Comprehensive approaches are needed that would identify bioactive components with evident activity against specific indications and provide a better link between science (ethno-botany, chemistry, biology and pharmacology) and market. Recently, the bark of black alder (Alnus glutinosa) appeared at market in the form of food supplement for treatment of different skin conditions. This study aimed to evaluate protective effects of two diarylheptanoids isolated from the bark of black alder: platyphylloside, 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-β-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-β-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2) towards doxorubicin damaging activity. To that end, we employed HaCaT cells, non-cancerous human keratinocytes commonly used for skin regenerative studies. Diarylheptanoids significantly antagonized the effects of doxorubicin by lowering the sensitivity of HaCaT cells to this drug. Compound 2 prevented doxorubicin-induced cell death by activating autophagy. Both 1 and 2 protected HaCaT cells against doxorubicin-induced DNA damage. They significantly promoted migration and affected F-actin distribution. These results indicate that chemo-protective effects of diarylheptanoids may occur at multiple subcellular levels. Therefore, diarylheptanoids 1 and 2 could be considered as protective agents for non-cancerous dividing cells during chemotherapy.",
publisher = "Elsevier",
journal = "Fitoterapia",
title = "Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes",
volume = "105",
doi = "10.1016/j.fitote.2015.07.003",
pages = "169-176"
}

Dinić, J., Ranđelović, T., Stanković, T., Dragoj, M., Isaković, A., Novaković, M.,& Pešić, M.. (2015). Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes. in Fitoterapia
Elsevier., 105, 169-176.
https://doi.org/10.1016/j.fitote.2015.07.003

Dinić J, Ranđelović T, Stanković T, Dragoj M, Isaković A, Novaković M, Pešić M. Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes. in Fitoterapia. 2015;105:169-176.
doi:10.1016/j.fitote.2015.07.003 .

Dinić, Jelena, Ranđelović, Teodora, Stanković, Tijana, Dragoj, Miodrag, Isaković, Aleksandra, Novaković, Miroslav, Pešić, Milica, "Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes" in Fitoterapia, 105 (2015):169-176,
https://doi.org/10.1016/j.fitote.2015.07.003 . .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Ranđelović, Teodora
AU  - Stanković, Tijana
AU  - Dragoj, Miodrag
AU  - Isaković, Aleksandra
AU  - Novaković, Miroslav
AU  - Pešić, Milica
PY  - 2015
UR  - https://www.sciencedirect.com/science/article/abs/pii/S0367326X1530040X
UR  - https://radar.ibiss.bg.ac.rs/123456789/3864
AB  - Medicinal plants are recognized from ancient times as a source of diverse therapeutic agents and many of them are used as dietary supplements. Comprehensive approaches are needed that would identify bioactive components with evident activity against specific indications and provide a better link between science (ethno-botany, chemistry, biology and pharmacology) and market. Recently, the bark of black alder (Alnus glutinosa) appeared at market in the form of food supplement for treatment of different skin conditions. This study aimed to evaluate protective effects of two diarylheptanoids isolated from the bark of black alder: platyphylloside, 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-β-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-β-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2) towards doxorubicin damaging activity. To that end, we employed HaCaT cells, non-cancerous human keratinocytes commonly used for skin regenerative studies. Diarylheptanoids significantly antagonized the effects of doxorubicin by lowering the sensitivity of HaCaT cells to this drug. Compound 2 prevented doxorubicin-induced cell death by activating autophagy. Both 1 and 2 protected HaCaT cells against doxorubicin-induced DNA damage. They significantly promoted migration and affected F-actin distribution. These results indicate that chemo-protective effects of diarylheptanoids may occur at multiple subcellular levels. Therefore, diarylheptanoids 1 and 2 could be considered as protective agents for non-cancerous dividing cells during chemotherapy.
PB  - Elsevier
T2  - Fitoterapia
T1  - Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes
VL  - 105
DO  - 10.1016/j.fitote.2015.07.003
SP  - 169
EP  - 176
ER  - 

@article{
author = "Dinić, Jelena and Ranđelović, Teodora and Stanković, Tijana and Dragoj, Miodrag and Isaković, Aleksandra and Novaković, Miroslav and Pešić, Milica",
year = "2015",
abstract = "Medicinal plants are recognized from ancient times as a source of diverse therapeutic agents and many of them are used as dietary supplements. Comprehensive approaches are needed that would identify bioactive components with evident activity against specific indications and provide a better link between science (ethno-botany, chemistry, biology and pharmacology) and market. Recently, the bark of black alder (Alnus glutinosa) appeared at market in the form of food supplement for treatment of different skin conditions. This study aimed to evaluate protective effects of two diarylheptanoids isolated from the bark of black alder: platyphylloside, 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-β-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-β-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2) towards doxorubicin damaging activity. To that end, we employed HaCaT cells, non-cancerous human keratinocytes commonly used for skin regenerative studies. Diarylheptanoids significantly antagonized the effects of doxorubicin by lowering the sensitivity of HaCaT cells to this drug. Compound 2 prevented doxorubicin-induced cell death by activating autophagy. Both 1 and 2 protected HaCaT cells against doxorubicin-induced DNA damage. They significantly promoted migration and affected F-actin distribution. These results indicate that chemo-protective effects of diarylheptanoids may occur at multiple subcellular levels. Therefore, diarylheptanoids 1 and 2 could be considered as protective agents for non-cancerous dividing cells during chemotherapy.",
publisher = "Elsevier",
journal = "Fitoterapia",
title = "Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes",
volume = "105",
doi = "10.1016/j.fitote.2015.07.003",
pages = "169-176"
}

Dinić, J., Ranđelović, T., Stanković, T., Dragoj, M., Isaković, A., Novaković, M.,& Pešić, M.. (2015). Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes. in Fitoterapia
Elsevier., 105, 169-176.
https://doi.org/10.1016/j.fitote.2015.07.003

Dinić J, Ranđelović T, Stanković T, Dragoj M, Isaković A, Novaković M, Pešić M. Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes. in Fitoterapia. 2015;105:169-176.
doi:10.1016/j.fitote.2015.07.003 .

Dinić, Jelena, Ranđelović, Teodora, Stanković, Tijana, Dragoj, Miodrag, Isaković, Aleksandra, Novaković, Miroslav, Pešić, Milica, "Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes" in Fitoterapia, 105 (2015):169-176,
https://doi.org/10.1016/j.fitote.2015.07.003 . .

TY  - JOUR
AU  - Džamić, Ana M.
AU  - Soković, Marina
AU  - Ristić, Mihailo S.
AU  - Novaković, Miroslav
AU  - Grujić-Jovanović, Slavica M.
AU  - Tešević, Vele
AU  - Marin, Petar D.
PY  - 2010
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/517
AB  - The present study describes the antifungal and antioxidant activity of Mentha longifolia (L.) Hudson essential oil. This plant is native to Europe, Central Asia and Australia. It is used as carminative, stomachic and stimulant and also in aromatherapy. The essential oil profile was determined by GC and GC-MS. The main compounds in the oil were trans-dihydrocarvone (23.64%), piperitone (17.33%) and cis-dihydrocarvone (15.68%). Minimum inhibitory concentrations (MIC) and minimum fungicidal concentrations (MFC) were recorded using the microdilution method. Commercial antimicotic bifonazol was used as a control. The concentration of 10 μl/ml showed fungicidal activity against Aspergillus and Fusarium species, Penicillium funiculosum and Trichoderma viride. Concentration of 5 μl/ml was efficient against Trichophyton menthagrophytes and yeast Candida albicans. The most sensitive micromycetes were Cladosporium fulvum, C. cladosporium cladosporioides and Penicillium ochrochloron where concentration of 2.5 μl/ml was lethal. The antioxidant activity of essential oil was evaluated by means of the 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging method. The essential oil of M. longifolia was able to reduce DPPH radicals into the DPPH-H form, and this activity was dose-dependent. The oil exhibited significant potential for antioxidant activity, and reduced DPPH to 50% (IC50=0,659 ml/ml of solution). .
AB  - U radu je ispitivano potencijalno delovanje etarskog ulja Mentha longifolia (L.) Huds. kao antifungalnog i antioksidativnog agensa. Vrsta M. longifolia je samonikla u Evropi, Centralnoj Aziji i Australiji. Koristi se kao karminativ, stomahik i stimulant u aromaterapiji. Kompozicija etarskog ulja je određivana korišćenjem gasne hromatografi je (GH) i gasne hromatografije sa masenom spektroskopijom (GH-MS). Dominantne komponente u ispitivanom etarskom ulju su: trans-dihidrokarvon (23.64%), piperiton (17.33%) i cis-dihidrokarvon (15.68%). Antifungalna aktivnost je ispitivana metodom mikrodilucije i određivane su minimalne inhibitorne i fungicidne koncentracije ulja i komercijalnog fungicida bifonazola. Etarsko ulje je pokazalo fungicidno dejstvo pri koncentraciji 10 μl/ml za gljive iz rodova Aspergillus i Fusarium kao i za vrste Penicillium funiculosum i Trichoderma viride. Najosetljivije su mikromicete Cladosporium fulvum, C. cladosporioides i Penicillium ochrochloron, za koje je letalna koncentracija 2.5 μl/ml. Antioksidativna aktivnost je rađena korišćenjem DPPH kao hvatača slobodnih radikala. Etarsko ulje M. longifolia je pokazalo sposobnost redukcije DPPH radikala u DPPH-H formu. Antifungalna aktivnost je predstavljena redukcijom DPPH na 50% (IC50=0,659 ml/ml rastvora).
T2  - Botanica Serbica
T1  - Antifungalna i antioksidativna aktivnost etarskog ulja Mentha longifolia (L.) Huds. (Lamiaceae)
T1  - Antifungal and antioxidant activity of Mentha longifolia (L.) Hudson (Lamiaceae) essential oil
IS  - 1
VL  - 34
SP  - 57
EP  - 61
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_517
ER  - 

@article{
author = "Džamić, Ana M. and Soković, Marina and Ristić, Mihailo S. and Novaković, Miroslav and Grujić-Jovanović, Slavica M. and Tešević, Vele and Marin, Petar D.",
year = "2010, 2010",
abstract = "The present study describes the antifungal and antioxidant activity of Mentha longifolia (L.) Hudson essential oil. This plant is native to Europe, Central Asia and Australia. It is used as carminative, stomachic and stimulant and also in aromatherapy. The essential oil profile was determined by GC and GC-MS. The main compounds in the oil were trans-dihydrocarvone (23.64%), piperitone (17.33%) and cis-dihydrocarvone (15.68%). Minimum inhibitory concentrations (MIC) and minimum fungicidal concentrations (MFC) were recorded using the microdilution method. Commercial antimicotic bifonazol was used as a control. The concentration of 10 μl/ml showed fungicidal activity against Aspergillus and Fusarium species, Penicillium funiculosum and Trichoderma viride. Concentration of 5 μl/ml was efficient against Trichophyton menthagrophytes and yeast Candida albicans. The most sensitive micromycetes were Cladosporium fulvum, C. cladosporium cladosporioides and Penicillium ochrochloron where concentration of 2.5 μl/ml was lethal. The antioxidant activity of essential oil was evaluated by means of the 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging method. The essential oil of M. longifolia was able to reduce DPPH radicals into the DPPH-H form, and this activity was dose-dependent. The oil exhibited significant potential for antioxidant activity, and reduced DPPH to 50% (IC50=0,659 ml/ml of solution). ., U radu je ispitivano potencijalno delovanje etarskog ulja Mentha longifolia (L.) Huds. kao antifungalnog i antioksidativnog agensa. Vrsta M. longifolia je samonikla u Evropi, Centralnoj Aziji i Australiji. Koristi se kao karminativ, stomahik i stimulant u aromaterapiji. Kompozicija etarskog ulja je određivana korišćenjem gasne hromatografi je (GH) i gasne hromatografije sa masenom spektroskopijom (GH-MS). Dominantne komponente u ispitivanom etarskom ulju su: trans-dihidrokarvon (23.64%), piperiton (17.33%) i cis-dihidrokarvon (15.68%). Antifungalna aktivnost je ispitivana metodom mikrodilucije i određivane su minimalne inhibitorne i fungicidne koncentracije ulja i komercijalnog fungicida bifonazola. Etarsko ulje je pokazalo fungicidno dejstvo pri koncentraciji 10 μl/ml za gljive iz rodova Aspergillus i Fusarium kao i za vrste Penicillium funiculosum i Trichoderma viride. Najosetljivije su mikromicete Cladosporium fulvum, C. cladosporioides i Penicillium ochrochloron, za koje je letalna koncentracija 2.5 μl/ml. Antioksidativna aktivnost je rađena korišćenjem DPPH kao hvatača slobodnih radikala. Etarsko ulje M. longifolia je pokazalo sposobnost redukcije DPPH radikala u DPPH-H formu. Antifungalna aktivnost je predstavljena redukcijom DPPH na 50% (IC50=0,659 ml/ml rastvora).",
journal = "Botanica Serbica",
title = "Antifungalna i antioksidativna aktivnost etarskog ulja Mentha longifolia (L.) Huds. (Lamiaceae), Antifungal and antioxidant activity of Mentha longifolia (L.) Hudson (Lamiaceae) essential oil",
number = "1",
volume = "34",
pages = "57-61",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_517"
}

Džamić, A. M., Soković, M., Ristić, M. S., Novaković, M., Grujić-Jovanović, S. M., Tešević, V.,& Marin, P. D.. (2010). Antifungalna i antioksidativna aktivnost etarskog ulja Mentha longifolia (L.) Huds. (Lamiaceae). in Botanica Serbica, 34(1), 57-61.
https://hdl.handle.net/21.15107/rcub_ibiss_517

Džamić AM, Soković M, Ristić MS, Novaković M, Grujić-Jovanović SM, Tešević V, Marin PD. Antifungalna i antioksidativna aktivnost etarskog ulja Mentha longifolia (L.) Huds. (Lamiaceae). in Botanica Serbica. 2010;34(1):57-61.
https://hdl.handle.net/21.15107/rcub_ibiss_517 .

Džamić, Ana M., Soković, Marina, Ristić, Mihailo S., Novaković, Miroslav, Grujić-Jovanović, Slavica M., Tešević, Vele, Marin, Petar D., "Antifungalna i antioksidativna aktivnost etarskog ulja Mentha longifolia (L.) Huds. (Lamiaceae)" in Botanica Serbica, 34, no. 1 (2010):57-61,
https://hdl.handle.net/21.15107/rcub_ibiss_517 .