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  - 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  - 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  - 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 .