TY  - JOUR
AU  - Jovanović Stojanov, Sofija
AU  - Ntungwe, Epole N.
AU  - Dinić, Jelena
AU  - Podolski-Renić, Ana
AU  - Pajović, Milica
AU  - Rijo, Patrícia
AU  - Pešić, Milica
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6027
AB  - Multidrug resistance in cancer is often mediated by P-glycoprotein. Natural compounds
have been suggested as a fourth generation of P-glycoprotein inhibitors. Coleon U, isolated from
Plectranthus mutabilis Codd., was reported to modulate P-glycoprotein activity but the underlying
mechanism has not yet been revealed. Therefore, the effects of Coleon U on cell viability, proliferation, and cell death induction were studied in a non-small-cell lung carcinoma model comprising
sensitive and multidrug-resistant cells with P-glycoprotein overexpression. P-glycoprotein activity
and mitochondrial membrane potential were assessed by flow cytometry upon Coleon U, sodiumorthovanadate (an ATPase inhibitor), and verapamil (an ATPase stimulator) treatments. SwissADME
was used to identify the pharmacokinetic properties of Coleon U, while P-glycoprotein expression
was studied by immunofluorescence. Our results showed that Coleon U is not a P-glycoprotein
substrate and is equally efficient in sensitive and multidrug-resistant cancer cells. A decrease in
P-glycoprotein activity observed with Coleon U and verapamil after 72 h is antagonized in combination with sodium-orthovanadate. Coleon U induced a pronounced effect on mitochondrial membrane
depolarization and showed a tendency to decrease P-glycoprotein expression. In conclusion, Coleon
U-delayed effect on the decrease in P-glycoprotein activity is due to P-glycoprotein’s functioning
dependence on ATP production in mitochondria.
PB  - Basel: MDPI
T2  - Pharmaceutics
T1  - Coleon U, Isolated from Plectranthus mutabilis Codd., Decreases P-Glycoprotein Activity Due to Mitochondrial Inhibition
IS  - 7
VL  - 15
DO  - 10.3390/pharmaceutics15071942
SP  - 1942
ER  - 

@article{
author = "Jovanović Stojanov, Sofija and Ntungwe, Epole N. and Dinić, Jelena and Podolski-Renić, Ana and Pajović, Milica and Rijo, Patrícia and Pešić, Milica",
year = "2023",
abstract = "Multidrug resistance in cancer is often mediated by P-glycoprotein. Natural compounds
have been suggested as a fourth generation of P-glycoprotein inhibitors. Coleon U, isolated from
Plectranthus mutabilis Codd., was reported to modulate P-glycoprotein activity but the underlying
mechanism has not yet been revealed. Therefore, the effects of Coleon U on cell viability, proliferation, and cell death induction were studied in a non-small-cell lung carcinoma model comprising
sensitive and multidrug-resistant cells with P-glycoprotein overexpression. P-glycoprotein activity
and mitochondrial membrane potential were assessed by flow cytometry upon Coleon U, sodiumorthovanadate (an ATPase inhibitor), and verapamil (an ATPase stimulator) treatments. SwissADME
was used to identify the pharmacokinetic properties of Coleon U, while P-glycoprotein expression
was studied by immunofluorescence. Our results showed that Coleon U is not a P-glycoprotein
substrate and is equally efficient in sensitive and multidrug-resistant cancer cells. A decrease in
P-glycoprotein activity observed with Coleon U and verapamil after 72 h is antagonized in combination with sodium-orthovanadate. Coleon U induced a pronounced effect on mitochondrial membrane
depolarization and showed a tendency to decrease P-glycoprotein expression. In conclusion, Coleon
U-delayed effect on the decrease in P-glycoprotein activity is due to P-glycoprotein’s functioning
dependence on ATP production in mitochondria.",
publisher = "Basel: MDPI",
journal = "Pharmaceutics",
title = "Coleon U, Isolated from Plectranthus mutabilis Codd., Decreases P-Glycoprotein Activity Due to Mitochondrial Inhibition",
number = "7",
volume = "15",
doi = "10.3390/pharmaceutics15071942",
pages = "1942"
}

Jovanović Stojanov, S., Ntungwe, E. N., Dinić, J., Podolski-Renić, A., Pajović, M., Rijo, P.,& Pešić, M.. (2023). Coleon U, Isolated from Plectranthus mutabilis Codd., Decreases P-Glycoprotein Activity Due to Mitochondrial Inhibition. in Pharmaceutics
Basel: MDPI., 15(7), 1942.
https://doi.org/10.3390/pharmaceutics15071942

Jovanović Stojanov S, Ntungwe EN, Dinić J, Podolski-Renić A, Pajović M, Rijo P, Pešić M. Coleon U, Isolated from Plectranthus mutabilis Codd., Decreases P-Glycoprotein Activity Due to Mitochondrial Inhibition. in Pharmaceutics. 2023;15(7):1942.
doi:10.3390/pharmaceutics15071942 .

Jovanović Stojanov, Sofija, Ntungwe, Epole N., Dinić, Jelena, Podolski-Renić, Ana, Pajović, Milica, Rijo, Patrícia, Pešić, Milica, "Coleon U, Isolated from Plectranthus mutabilis Codd., Decreases P-Glycoprotein Activity Due to Mitochondrial Inhibition" in Pharmaceutics, 15, no. 7 (2023):1942,
https://doi.org/10.3390/pharmaceutics15071942 . .

TY  - JOUR
AU  - Ntungwe, Epole N.
AU  - Jovanović Stojanov, Sofija
AU  - Duarte, Noélia M.
AU  - Candeias, Nuno R.
AU  - Díaz-Lanza, Ana M.
AU  - Vágvölgyi, Máté
AU  - Hunyadi, Attila
AU  - Pešić, Milica
AU  - Rijo, Patrícia
PY  - 2022
UR  - https://pubs.acs.org/doi/10.1021/acsmedchemlett.1c00711
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9014510
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4945
AB  - In this study, a bioguided fractionation of Plectranthus mutabilis extract was performed by chromatographic methods. It yielded one new nor-abietane diterpene, mutabilol (1), and three known abietanes, coleon-U-quinone (2), 8α,9α-epoxycoleon-U-quinone (3), and coleon U (4). The abietane diterpenoid 5 was also tentatively identified using HPLC-MS/MS. Moreover, the extract profile and quantification of each isolated compound were determined by HPLC-DAD. Compound 4 was the major compound in the extract. Compounds 2-4 were found to be selective toward cancer cell lines and were able to inhibit P-glycoprotein (P-gp) activity in NCI-H460/R cells at longer exposure of 72 h and consequently revert doxorubicin (DOX) resistance in subsequent combined treatment. None of the compounds influenced the P-gp expression in NCI-H460/R cells, while the extract significantly increased it.
T2  - ACS Medicinal Chemistry Letters
T1  - C20-nor-Abietane and Three Abietane Diterpenoids from Plectranthus mutabilis Leaves as P-Glycoprotein Modulators.
IS  - 4
VL  - 13
DO  - 10.1021/acsmedchemlett.1c00711
SP  - 674
EP  - 680
ER  - 

@article{
author = "Ntungwe, Epole N. and Jovanović Stojanov, Sofija and Duarte, Noélia M. and Candeias, Nuno R. and Díaz-Lanza, Ana M. and Vágvölgyi, Máté and Hunyadi, Attila and Pešić, Milica and Rijo, Patrícia",
year = "2022",
abstract = "In this study, a bioguided fractionation of Plectranthus mutabilis extract was performed by chromatographic methods. It yielded one new nor-abietane diterpene, mutabilol (1), and three known abietanes, coleon-U-quinone (2), 8α,9α-epoxycoleon-U-quinone (3), and coleon U (4). The abietane diterpenoid 5 was also tentatively identified using HPLC-MS/MS. Moreover, the extract profile and quantification of each isolated compound were determined by HPLC-DAD. Compound 4 was the major compound in the extract. Compounds 2-4 were found to be selective toward cancer cell lines and were able to inhibit P-glycoprotein (P-gp) activity in NCI-H460/R cells at longer exposure of 72 h and consequently revert doxorubicin (DOX) resistance in subsequent combined treatment. None of the compounds influenced the P-gp expression in NCI-H460/R cells, while the extract significantly increased it.",
journal = "ACS Medicinal Chemistry Letters",
title = "C20-nor-Abietane and Three Abietane Diterpenoids from Plectranthus mutabilis Leaves as P-Glycoprotein Modulators.",
number = "4",
volume = "13",
doi = "10.1021/acsmedchemlett.1c00711",
pages = "674-680"
}

Ntungwe, E. N., Jovanović Stojanov, S., Duarte, N. M., Candeias, N. R., Díaz-Lanza, A. M., Vágvölgyi, M., Hunyadi, A., Pešić, M.,& Rijo, P.. (2022). C20-nor-Abietane and Three Abietane Diterpenoids from Plectranthus mutabilis Leaves as P-Glycoprotein Modulators.. in ACS Medicinal Chemistry Letters, 13(4), 674-680.
https://doi.org/10.1021/acsmedchemlett.1c00711

Ntungwe EN, Jovanović Stojanov S, Duarte NM, Candeias NR, Díaz-Lanza AM, Vágvölgyi M, Hunyadi A, Pešić M, Rijo P. C20-nor-Abietane and Three Abietane Diterpenoids from Plectranthus mutabilis Leaves as P-Glycoprotein Modulators.. in ACS Medicinal Chemistry Letters. 2022;13(4):674-680.
doi:10.1021/acsmedchemlett.1c00711 .

Ntungwe, Epole N., Jovanović Stojanov, Sofija, Duarte, Noélia M., Candeias, Nuno R., Díaz-Lanza, Ana M., Vágvölgyi, Máté, Hunyadi, Attila, Pešić, Milica, Rijo, Patrícia, "C20-nor-Abietane and Three Abietane Diterpenoids from Plectranthus mutabilis Leaves as P-Glycoprotein Modulators." in ACS Medicinal Chemistry Letters, 13, no. 4 (2022):674-680,
https://doi.org/10.1021/acsmedchemlett.1c00711 . .

TY  - CONF
AU  - Isca, Vera
AU  - Bangay, Gabrielle
AU  - Princiotto, Salvatore
AU  - Dinić, Jelena
AU  - Pešić, Milica
AU  - Saraíva, Lucília
AU  - Afonso, Carlos
AU  - Rijo, Patrícia
PY  - 2022
UR  - https://stratagem-cost.eu/wp-content/uploads/2022/07/Abstract-Book-Coimbra.pdf
UR  - https://stratagem-cost.eu/2022/04/stratagems-5th-co-located-annual-conference-and-wg3-4-training-school-to-be-held-in-coimbra-portugal-june-july-2022/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5622
AB  - Plectranthus genus (Lamiaceae family) is widely used in traditional medicine, and the presence of
pharmacologically active compounds, specifically diterpenes, is well reported. The cytotoxic diterpene
royleanones 7α-acetoxy-6β-hydroxyroyleanone (Roy) and 6,7-dehydroroyleanone (DeRoy) are the
major compounds of P. grandidentatus Gürke (acetonic extract) and P. madagascariensis (Pers.) Benth.
(essential oil), respectively. In this work, Roy and DeRoy were investigated as potential antitumor
agents through the activation of protein kinase C (PKC) isoforms (α, βI, δ, ε and ζ) and inhibition of
the efflux pump, P-glycoprotein (P-gp). Additionally, the reactivity of Roy and DeRoy was explored
to synthesize a library of new derivatives to be also evaluated as cytotoxic agents. PKC-α, βI, δ, ε, and
ζ activation was tested on a yeast-based screening assay. Interestingly, one benzoylated derivative
showed selective PKC-δ activation, while DeRoy exhibited enhanced PKC activity in all tested
isoforms, compared to the positive control. Moreover, inhibition of P-gp activity was evaluated in
human non-small cell lung carcinoma NCI-H460 and its MDR counterpart NCI-H460/R. It was
possible to identify an analogue with P-gp inhibitory activity higher than the natural diterpenes Roy
and DeRoy, and comparable to Dexverapamil (positive control). Several other semi-synthetic
products are currently under investigation as potential chemotherapeutic agents.
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  - Cytotoxic Activity of diterpenes from Plectranthus spp. for MDR cancer therapy
SP  - 73
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5622
ER  - 

@conference{
author = "Isca, Vera and Bangay, Gabrielle and Princiotto, Salvatore and Dinić, Jelena and Pešić, Milica and Saraíva, Lucília and Afonso, Carlos and Rijo, Patrícia",
year = "2022",
abstract = "Plectranthus genus (Lamiaceae family) is widely used in traditional medicine, and the presence of
pharmacologically active compounds, specifically diterpenes, is well reported. The cytotoxic diterpene
royleanones 7α-acetoxy-6β-hydroxyroyleanone (Roy) and 6,7-dehydroroyleanone (DeRoy) are the
major compounds of P. grandidentatus Gürke (acetonic extract) and P. madagascariensis (Pers.) Benth.
(essential oil), respectively. In this work, Roy and DeRoy were investigated as potential antitumor
agents through the activation of protein kinase C (PKC) isoforms (α, βI, δ, ε and ζ) and inhibition of
the efflux pump, P-glycoprotein (P-gp). Additionally, the reactivity of Roy and DeRoy was explored
to synthesize a library of new derivatives to be also evaluated as cytotoxic agents. PKC-α, βI, δ, ε, and
ζ activation was tested on a yeast-based screening assay. Interestingly, one benzoylated derivative
showed selective PKC-δ activation, while DeRoy exhibited enhanced PKC activity in all tested
isoforms, compared to the positive control. Moreover, inhibition of P-gp activity was evaluated in
human non-small cell lung carcinoma NCI-H460 and its MDR counterpart NCI-H460/R. It was
possible to identify an analogue with P-gp inhibitory activity higher than the natural diterpenes Roy
and DeRoy, and comparable to Dexverapamil (positive control). Several other semi-synthetic
products are currently under investigation as potential chemotherapeutic agents.",
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 = "Cytotoxic Activity of diterpenes from Plectranthus spp. for MDR cancer therapy",
pages = "73",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5622"
}

Isca, V., Bangay, G., Princiotto, S., Dinić, J., Pešić, M., Saraíva, L., Afonso, C.,& Rijo, P.. (2022). Cytotoxic Activity of diterpenes from Plectranthus spp. for MDR cancer therapy. 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., 73.
https://hdl.handle.net/21.15107/rcub_ibiss_5622

Isca V, Bangay G, Princiotto S, Dinić J, Pešić M, Saraíva L, Afonso C, Rijo P. Cytotoxic Activity of diterpenes from Plectranthus spp. for MDR cancer therapy. 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;:73.
https://hdl.handle.net/21.15107/rcub_ibiss_5622 .

Isca, Vera, Bangay, Gabrielle, Princiotto, Salvatore, Dinić, Jelena, Pešić, Milica, Saraíva, Lucília, Afonso, Carlos, Rijo, Patrícia, "Cytotoxic Activity of diterpenes from Plectranthus spp. for MDR cancer therapy" 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):73,
https://hdl.handle.net/21.15107/rcub_ibiss_5622 .

TY  - CONF
AU  - Ntungwe, Epole
AU  - Jovanović Stojanov, Sofija
AU  - Duarte, Noélia
AU  - R. Candeias, Nuno
AU  - Díaz-Lanza, Ana María
AU  - Pešić, Milica
AU  - Rijo, Patrícia
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5610
UR  - https://sciforum.net/paper/view/13460
AB  - The development of multidrug resistance (MDR) is one of the major challenges in the successful treatment of cancer. MDR is often associated with the P-glycoprotein efflux pump. Natural products are a source of promising lead compounds to overcome MDR and, among them, diterpenoids from Plectranthus spp. are known as P-gp modulators. Bioguided fractionation of P. mutabilis acetone extract led to the isolation of one new nor-abietane diterpene, mutabilol (1), and three coleon compounds (coleon-U-quinone (2), 8α,9α-epoxycoleon-U-quinone (3), and coleon U (4)). Moreover, an additional acetoxy derivative of an abietane diterpenoid was tentatively identified using HPLC-MS/MS. The compounds were quantified using HPLC-DAD and coleon U was found to be the major compound in the extract. Using computational studies, a biosynthetic relationship between compounds 2 - 4 revealed that both compounds 2 and 3 were formed directly from compound 4. Compounds 2 - 4 were found to be selective towards the cancer cell lines and their anticancer effect was not compromised by the P-gp activity in resistant NCI-H460/R cells. Importantly 2, 3, and 4 were able to inhibit P-gp activity in NCI-H460/R cells at longer exposure (72 h) and revert doxorubicin (DOX) resistance in combined treatment. None of the compounds influenced the P-gp expression in NCI-H460/R cells, while the extract significantly increased it. Our study identified abietane diterpenoids from P. mutabilis that can evade MDR in cancer cells and inhibit the P-gp activity in prolonged treatment.
PB  - SCIForum
C3  - The 8th International Electronic Conference on Medicinal Chemistry; 2022 Nov 1-30; Virtual Event
T1  - P-gp modulation and biosynthetic relationship of isolated compounds from Plectranthus mutabilis Codd.
DO  - 10.3390/ECMC2022-13460
ER  - 

@conference{
author = "Ntungwe, Epole and Jovanović Stojanov, Sofija and Duarte, Noélia and R. Candeias, Nuno and Díaz-Lanza, Ana María and Pešić, Milica and Rijo, Patrícia",
year = "2022",
abstract = "The development of multidrug resistance (MDR) is one of the major challenges in the successful treatment of cancer. MDR is often associated with the P-glycoprotein efflux pump. Natural products are a source of promising lead compounds to overcome MDR and, among them, diterpenoids from Plectranthus spp. are known as P-gp modulators. Bioguided fractionation of P. mutabilis acetone extract led to the isolation of one new nor-abietane diterpene, mutabilol (1), and three coleon compounds (coleon-U-quinone (2), 8α,9α-epoxycoleon-U-quinone (3), and coleon U (4)). Moreover, an additional acetoxy derivative of an abietane diterpenoid was tentatively identified using HPLC-MS/MS. The compounds were quantified using HPLC-DAD and coleon U was found to be the major compound in the extract. Using computational studies, a biosynthetic relationship between compounds 2 - 4 revealed that both compounds 2 and 3 were formed directly from compound 4. Compounds 2 - 4 were found to be selective towards the cancer cell lines and their anticancer effect was not compromised by the P-gp activity in resistant NCI-H460/R cells. Importantly 2, 3, and 4 were able to inhibit P-gp activity in NCI-H460/R cells at longer exposure (72 h) and revert doxorubicin (DOX) resistance in combined treatment. None of the compounds influenced the P-gp expression in NCI-H460/R cells, while the extract significantly increased it. Our study identified abietane diterpenoids from P. mutabilis that can evade MDR in cancer cells and inhibit the P-gp activity in prolonged treatment.",
publisher = "SCIForum",
journal = "The 8th International Electronic Conference on Medicinal Chemistry; 2022 Nov 1-30; Virtual Event",
title = "P-gp modulation and biosynthetic relationship of isolated compounds from Plectranthus mutabilis Codd.",
doi = "10.3390/ECMC2022-13460"
}

Ntungwe, E., Jovanović Stojanov, S., Duarte, N., R. Candeias, N., Díaz-Lanza, A. M., Pešić, M.,& Rijo, P.. (2022). P-gp modulation and biosynthetic relationship of isolated compounds from Plectranthus mutabilis Codd.. in The 8th International Electronic Conference on Medicinal Chemistry; 2022 Nov 1-30; Virtual Event
SCIForum..
https://doi.org/10.3390/ECMC2022-13460

Ntungwe E, Jovanović Stojanov S, Duarte N, R. Candeias N, Díaz-Lanza AM, Pešić M, Rijo P. P-gp modulation and biosynthetic relationship of isolated compounds from Plectranthus mutabilis Codd.. in The 8th International Electronic Conference on Medicinal Chemistry; 2022 Nov 1-30; Virtual Event. 2022;.
doi:10.3390/ECMC2022-13460 .

Ntungwe, Epole, Jovanović Stojanov, Sofija, Duarte, Noélia, R. Candeias, Nuno, Díaz-Lanza, Ana María, Pešić, Milica, Rijo, Patrícia, "P-gp modulation and biosynthetic relationship of isolated compounds from Plectranthus mutabilis Codd." in The 8th International Electronic Conference on Medicinal Chemistry; 2022 Nov 1-30; Virtual Event (2022),
https://doi.org/10.3390/ECMC2022-13460 . .

TY  - JOUR
AU  - Neto, Iris
AU  - Domínguez-Martín, Eva María
AU  - Ntungwe, Epole
AU  - Reis, Catarina
AU  - Pešić, Milica
AU  - Faustino, Célia
AU  - Rijo, Patrícia
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4262
AB  - The antimicrobial activity of dehydroabietic acid (DHA) for its use as an antibiofilm agent was tested in this work. DHA was assayed against a collection of Gram-positive, Gram-negative sensitive and resistant bacteria and yeasts through the minimum inhibitory concentration (MIC), MIC with Bioburden challenge, minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC), MBIC with Bioburden challenge and growth curve studies. Toxicological studies (Artemia salina, sulforhodamine B (SRB) assay) were done to assess if the compound had antimicrobial and not cytotoxic properties. Furthermore, microencapsulation and stability studies were carried out to evaluate the chemical behavior and stability of DHA. On MIC results, Gram-positive bacteria Staphylococcus aureus ATCC 1228 and Mycobacterium smegmatis ATCC 607 presented a high efficiency (7.81 µg/mL), while on Gram-negative bacteria the highest MIC value of 125 µg/mL was obtained by all Klebsiella pneumoniae strains and Escherichia coli isolate strain HSM 303. Bioburden challenge showed that MIC, MBIC and percentage biofilm inhibition (BI) values suffered alterations, therefore, having higher concentrations. MBIC values demonstrated that DHA has a higher efficiency against S. aureus ATCC 43866 with a percentage of BI of 75.13 ± 0.82% at 0.49 µg/mL. Growth curve kinetic profiles of DHA against S. aureus ATCC 25923 were observed to be bacteriostatic. DHA-alginate beads had a average size of 2.37 ± 0.20 and 2.31 ± 0.17 × 103 µm2 with an encapsulation efficiency (EE%) around 99.49 ± 0.05%, a protection percentage (PP%) of 60.00 ± 0.05% in the gastric environment and a protection efficiency (PE%) around 88.12 ± 0.05% against UV light. In toxicological studies DHA has shown IC50 of 19.59 ± 7.40 µg/mL and a LC50 of 21.71 ± 2.18%. The obtained results indicate that DHA is a promising antimicrobial candidate against a wide range of bacteria and biofilm formation that must be further explored.
PB  - Basel : MDPI
T2  - Pharmaceutics
T1  - Dehydroabietic Acid Microencapsulation Potential as Biofilm-Mediated Infections Treatment
IS  - 6
VL  - 13
DO  - 10.3390/pharmaceutics13060825
SP  - 825
ER  - 

@article{
author = "Neto, Iris and Domínguez-Martín, Eva María and Ntungwe, Epole and Reis, Catarina and Pešić, Milica and Faustino, Célia and Rijo, Patrícia",
year = "2021",
abstract = "The antimicrobial activity of dehydroabietic acid (DHA) for its use as an antibiofilm agent was tested in this work. DHA was assayed against a collection of Gram-positive, Gram-negative sensitive and resistant bacteria and yeasts through the minimum inhibitory concentration (MIC), MIC with Bioburden challenge, minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC), MBIC with Bioburden challenge and growth curve studies. Toxicological studies (Artemia salina, sulforhodamine B (SRB) assay) were done to assess if the compound had antimicrobial and not cytotoxic properties. Furthermore, microencapsulation and stability studies were carried out to evaluate the chemical behavior and stability of DHA. On MIC results, Gram-positive bacteria Staphylococcus aureus ATCC 1228 and Mycobacterium smegmatis ATCC 607 presented a high efficiency (7.81 µg/mL), while on Gram-negative bacteria the highest MIC value of 125 µg/mL was obtained by all Klebsiella pneumoniae strains and Escherichia coli isolate strain HSM 303. Bioburden challenge showed that MIC, MBIC and percentage biofilm inhibition (BI) values suffered alterations, therefore, having higher concentrations. MBIC values demonstrated that DHA has a higher efficiency against S. aureus ATCC 43866 with a percentage of BI of 75.13 ± 0.82% at 0.49 µg/mL. Growth curve kinetic profiles of DHA against S. aureus ATCC 25923 were observed to be bacteriostatic. DHA-alginate beads had a average size of 2.37 ± 0.20 and 2.31 ± 0.17 × 103 µm2 with an encapsulation efficiency (EE%) around 99.49 ± 0.05%, a protection percentage (PP%) of 60.00 ± 0.05% in the gastric environment and a protection efficiency (PE%) around 88.12 ± 0.05% against UV light. In toxicological studies DHA has shown IC50 of 19.59 ± 7.40 µg/mL and a LC50 of 21.71 ± 2.18%. The obtained results indicate that DHA is a promising antimicrobial candidate against a wide range of bacteria and biofilm formation that must be further explored.",
publisher = "Basel : MDPI",
journal = "Pharmaceutics",
title = "Dehydroabietic Acid Microencapsulation Potential as Biofilm-Mediated Infections Treatment",
number = "6",
volume = "13",
doi = "10.3390/pharmaceutics13060825",
pages = "825"
}

Neto, I., Domínguez-Martín, E. M., Ntungwe, E., Reis, C., Pešić, M., Faustino, C.,& Rijo, P.. (2021). Dehydroabietic Acid Microencapsulation Potential as Biofilm-Mediated Infections Treatment. in Pharmaceutics
Basel : MDPI., 13(6), 825.
https://doi.org/10.3390/pharmaceutics13060825

Neto I, Domínguez-Martín EM, Ntungwe E, Reis C, Pešić M, Faustino C, Rijo P. Dehydroabietic Acid Microencapsulation Potential as Biofilm-Mediated Infections Treatment. in Pharmaceutics. 2021;13(6):825.
doi:10.3390/pharmaceutics13060825 .

Neto, Iris, Domínguez-Martín, Eva María, Ntungwe, Epole, Reis, Catarina, Pešić, Milica, Faustino, Célia, Rijo, Patrícia, "Dehydroabietic Acid Microencapsulation Potential as Biofilm-Mediated Infections Treatment" in Pharmaceutics, 13, no. 6 (2021):825,
https://doi.org/10.3390/pharmaceutics13060825 . .

TY  - JOUR
AU  - Rijo, Patrícia
AU  - Pešić, Milica
AU  - Fernandes, Ana S.
AU  - Santos, Cláudia N.
PY  - 2020
UR  - https://www.hindawi.com/journals/omcl/2020/2407074/
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3718
T2  - Oxidative Medicine and Cellular Longevity
T1  - Natural Products: Optimizing Cancer Treatment through Modulation of Redox Balance
VL  - 2020
DO  - 10.1155/2020/2407074
SP  - 2407074
ER  - 

@article{
author = "Rijo, Patrícia and Pešić, Milica and Fernandes, Ana S. and Santos, Cláudia N.",
year = "2020",
journal = "Oxidative Medicine and Cellular Longevity",
title = "Natural Products: Optimizing Cancer Treatment through Modulation of Redox Balance",
volume = "2020",
doi = "10.1155/2020/2407074",
pages = "2407074"
}

Rijo, P., Pešić, M., Fernandes, A. S.,& Santos, C. N.. (2020). Natural Products: Optimizing Cancer Treatment through Modulation of Redox Balance. in Oxidative Medicine and Cellular Longevity, 2020, 2407074.
https://doi.org/10.1155/2020/2407074

Rijo P, Pešić M, Fernandes AS, Santos CN. Natural Products: Optimizing Cancer Treatment through Modulation of Redox Balance. in Oxidative Medicine and Cellular Longevity. 2020;2020:2407074.
doi:10.1155/2020/2407074 .

Rijo, Patrícia, Pešić, Milica, Fernandes, Ana S., Santos, Cláudia N., "Natural Products: Optimizing Cancer Treatment through Modulation of Redox Balance" in Oxidative Medicine and Cellular Longevity, 2020 (2020):2407074,
https://doi.org/10.1155/2020/2407074 . .

TY  - JOUR
AU  - Garcia, Catarina
AU  - Isca, Vera
AU  - Pereira, Filipe
AU  - Monteiro, Carlos
AU  - Ntungwe, Epole
AU  - Sousa, Francisco
AU  - Dinić, Jelena
AU  - Holmstedt, Suvi
AU  - Roberto, Amílcar
AU  - Díaz-Lanza, Ana
AU  - Reis, Catarina
AU  - Pešić, Milica
AU  - Candeias, Nuno
AU  - Ferreira, Ricardo
AU  - Duarte, Noélia
AU  - Afonso, Carlos
AU  - Rijo, Patrícia
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4261
AB  - Cancer is among the leading causes of death worldwide. One of the most challenging obstacles in cancer treatment is multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp) is associated with MDR. The growing incidence of cancer and the development of MDR drive the search for novel and more effective anticancer drugs to overcome the MDR problem. Royleanones are natural bioactive compounds frequently found in Plectranthus spp. The cytotoxic diterpene 6,7-dehydroroyleanone (1) is the main component of the P. madagascariensis (Pers.) Benth. essential oil, while 7α-acetoxy-6β-hydroxyroyleanone (2) can be isolated from acetonic extracts of P. grandidentatus Gürke. The reactivity of the natural royleanones 1 and 2 was explored to obtain a small library of new P-gp inhibitors. Four new derivatives (6,7-dehydro-12-O-tert-butyl-carbonate-royleanone (20), 6,7-dehydro-12-O-methylroyleanone (21), 6,7-dehydro-12-O-benzoylroyleanone (22), and 7α-acetoxy-6β-hydroxy-12-O-benzoylroyleanone (23) were obtained as pure with overall modest to excellent yields (21-97%). P-gp inhibition potential of the derivatives 20-23 was evaluated in human non-small cell lung carcinoma NCI-H460 and its MDR counterpart NCI-H460/R with the P-gp overexpression, through MTT assay. Previously prepared diterpene 7α-acetoxy-6β-benzoyloxy-12-O-(4-chloro)benzoylroyleanone (4), has also been tested. The P-gp inhibiting effects of compounds 1-4 were also assessed through a Rhodamine 123 accumulation assay. Derivatives 4 and 23 have significant P-gp inhibitory potential. Regarding stability and P-gp inhibition potential, results suggest that the formation of benzoyl esters is a more convenient approach for future derivatives with enhanced effect on the cell viability decrease. Compound 4 presented higher anti-P-gp potential than the natural diterpenes 1, 2, and 3, with comparable inhibitory potential to Dexverapamil. Moreover, derivative 4 showed the ability to sensitize the resistant NCI-H460/R cells to doxorubicin.
PB  - Lausanne : Frontiers
T2  - Frontiers in Pharmacology
T1  - Royleanone Derivatives From Plectranthus spp. as a Novel Class of P-Glycoprotein Inhibitors
VL  - 11
DO  - 10.3389/fphar.2020.557789
SP  - 557789
ER  - 

@article{
author = "Garcia, Catarina and Isca, Vera and Pereira, Filipe and Monteiro, Carlos and Ntungwe, Epole and Sousa, Francisco and Dinić, Jelena and Holmstedt, Suvi and Roberto, Amílcar and Díaz-Lanza, Ana and Reis, Catarina and Pešić, Milica and Candeias, Nuno and Ferreira, Ricardo and Duarte, Noélia and Afonso, Carlos and Rijo, Patrícia",
year = "2020",
abstract = "Cancer is among the leading causes of death worldwide. One of the most challenging obstacles in cancer treatment is multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp) is associated with MDR. The growing incidence of cancer and the development of MDR drive the search for novel and more effective anticancer drugs to overcome the MDR problem. Royleanones are natural bioactive compounds frequently found in Plectranthus spp. The cytotoxic diterpene 6,7-dehydroroyleanone (1) is the main component of the P. madagascariensis (Pers.) Benth. essential oil, while 7α-acetoxy-6β-hydroxyroyleanone (2) can be isolated from acetonic extracts of P. grandidentatus Gürke. The reactivity of the natural royleanones 1 and 2 was explored to obtain a small library of new P-gp inhibitors. Four new derivatives (6,7-dehydro-12-O-tert-butyl-carbonate-royleanone (20), 6,7-dehydro-12-O-methylroyleanone (21), 6,7-dehydro-12-O-benzoylroyleanone (22), and 7α-acetoxy-6β-hydroxy-12-O-benzoylroyleanone (23) were obtained as pure with overall modest to excellent yields (21-97%). P-gp inhibition potential of the derivatives 20-23 was evaluated in human non-small cell lung carcinoma NCI-H460 and its MDR counterpart NCI-H460/R with the P-gp overexpression, through MTT assay. Previously prepared diterpene 7α-acetoxy-6β-benzoyloxy-12-O-(4-chloro)benzoylroyleanone (4), has also been tested. The P-gp inhibiting effects of compounds 1-4 were also assessed through a Rhodamine 123 accumulation assay. Derivatives 4 and 23 have significant P-gp inhibitory potential. Regarding stability and P-gp inhibition potential, results suggest that the formation of benzoyl esters is a more convenient approach for future derivatives with enhanced effect on the cell viability decrease. Compound 4 presented higher anti-P-gp potential than the natural diterpenes 1, 2, and 3, with comparable inhibitory potential to Dexverapamil. Moreover, derivative 4 showed the ability to sensitize the resistant NCI-H460/R cells to doxorubicin.",
publisher = "Lausanne : Frontiers",
journal = "Frontiers in Pharmacology",
title = "Royleanone Derivatives From Plectranthus spp. as a Novel Class of P-Glycoprotein Inhibitors",
volume = "11",
doi = "10.3389/fphar.2020.557789",
pages = "557789"
}

Garcia, C., Isca, V., Pereira, F., Monteiro, C., Ntungwe, E., Sousa, F., Dinić, J., Holmstedt, S., Roberto, A., Díaz-Lanza, A., Reis, C., Pešić, M., Candeias, N., Ferreira, R., Duarte, N., Afonso, C.,& Rijo, P.. (2020). Royleanone Derivatives From Plectranthus spp. as a Novel Class of P-Glycoprotein Inhibitors. in Frontiers in Pharmacology
Lausanne : Frontiers., 11, 557789.
https://doi.org/10.3389/fphar.2020.557789

Garcia C, Isca V, Pereira F, Monteiro C, Ntungwe E, Sousa F, Dinić J, Holmstedt S, Roberto A, Díaz-Lanza A, Reis C, Pešić M, Candeias N, Ferreira R, Duarte N, Afonso C, Rijo P. Royleanone Derivatives From Plectranthus spp. as a Novel Class of P-Glycoprotein Inhibitors. in Frontiers in Pharmacology. 2020;11:557789.
doi:10.3389/fphar.2020.557789 .

Garcia, Catarina, Isca, Vera, Pereira, Filipe, Monteiro, Carlos, Ntungwe, Epole, Sousa, Francisco, Dinić, Jelena, Holmstedt, Suvi, Roberto, Amílcar, Díaz-Lanza, Ana, Reis, Catarina, Pešić, Milica, Candeias, Nuno, Ferreira, Ricardo, Duarte, Noélia, Afonso, Carlos, Rijo, Patrícia, "Royleanone Derivatives From Plectranthus spp. as a Novel Class of P-Glycoprotein Inhibitors" in Frontiers in Pharmacology, 11 (2020):557789,
https://doi.org/10.3389/fphar.2020.557789 . .

TY  - JOUR
AU  - Isca, Vera M. S.
AU  - Ferreira, Ricardo J.
AU  - Garcia, Catarina
AU  - Monteiro, Carlos M.
AU  - Dinić, Jelena
AU  - Holmstedt, Suvi
AU  - André, Vânia
AU  - Pešić, Milica
AU  - Dos Santos, Daniel J. V. A.
AU  - Candeias, Nuno R.
AU  - Afonso, Carlos A. M.
AU  - Rijo, Patrícia
PY  - 2020
UR  - https://pubs.acs.org/doi/10.1021/acsmedchemlett.9b00642
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3820
AB  - The development of multidrug resistance (MDR) is a major cause of failure in cancer chemotherapy. Several abietane diterpenes with antitumoral activities have been isolated from Plectranthus spp. such as 6,7-dehydroroyleanone (DHR, 1) and 7α-acetoxy-6β-hydroxyroyleanone (AHR, 2). Several royleanone derivatives were prepared through hemisynthesis from natural compounds 1 and 2 to achieve a small library of products with enhanced anti-P-glycoprotein activity. Nonetheless, some derivatives tend to be unstable. Therefore, to reason such lack of stability, the electron density based local reactivity descriptors condensed Fukui functions and dual descriptor were calculated for several derivatives of DHR. Additionally, molecular docking and molecular dynamics studies were performed on several other derivatives to clarify the molecular mechanisms by which they may exert their inhibitory effect in P-gp activity. The analysis on local reactivity descriptors was important to understand possible degradation pathways and to guide further synthetic approaches toward new royleanone derivatives. A molecular docking study suggested that the presence of aromatic moieties increases the binding affinity of royleanone derivatives toward P-gp. It further suggests that one royleanone benzoylated derivative may act as a noncompetitive efflux modulator when bound to the M-site. The future generation of novel royleanone derivatives will involve (i) a selective modification of position C-12 with chemical moieties smaller than unsubstituted benzoyl rings and (ii) the modification of the substitution pattern of the benzoyloxy moiety at position C-6.
PB  - Washington : ACS Publications
T2  - ACS Medicinal Chemistry Letters
T1  - Molecular Docking Studies of Royleanone Diterpenoids from Plectranthus spp. as P-Glycoprotein Inhibitors
IS  - 5
VL  - 11
DO  - 10.1021/acsmedchemlett.9b00642
SP  - 839
EP  - 845
ER  - 

@article{
author = "Isca, Vera M. S. and Ferreira, Ricardo J. and Garcia, Catarina and Monteiro, Carlos M. and Dinić, Jelena and Holmstedt, Suvi and André, Vânia and Pešić, Milica and Dos Santos, Daniel J. V. A. and Candeias, Nuno R. and Afonso, Carlos A. M. and Rijo, Patrícia",
year = "2020",
abstract = "The development of multidrug resistance (MDR) is a major cause of failure in cancer chemotherapy. Several abietane diterpenes with antitumoral activities have been isolated from Plectranthus spp. such as 6,7-dehydroroyleanone (DHR, 1) and 7α-acetoxy-6β-hydroxyroyleanone (AHR, 2). Several royleanone derivatives were prepared through hemisynthesis from natural compounds 1 and 2 to achieve a small library of products with enhanced anti-P-glycoprotein activity. Nonetheless, some derivatives tend to be unstable. Therefore, to reason such lack of stability, the electron density based local reactivity descriptors condensed Fukui functions and dual descriptor were calculated for several derivatives of DHR. Additionally, molecular docking and molecular dynamics studies were performed on several other derivatives to clarify the molecular mechanisms by which they may exert their inhibitory effect in P-gp activity. The analysis on local reactivity descriptors was important to understand possible degradation pathways and to guide further synthetic approaches toward new royleanone derivatives. A molecular docking study suggested that the presence of aromatic moieties increases the binding affinity of royleanone derivatives toward P-gp. It further suggests that one royleanone benzoylated derivative may act as a noncompetitive efflux modulator when bound to the M-site. The future generation of novel royleanone derivatives will involve (i) a selective modification of position C-12 with chemical moieties smaller than unsubstituted benzoyl rings and (ii) the modification of the substitution pattern of the benzoyloxy moiety at position C-6.",
publisher = "Washington : ACS Publications",
journal = "ACS Medicinal Chemistry Letters",
title = "Molecular Docking Studies of Royleanone Diterpenoids from Plectranthus spp. as P-Glycoprotein Inhibitors",
number = "5",
volume = "11",
doi = "10.1021/acsmedchemlett.9b00642",
pages = "839-845"
}

Isca, V. M. S., Ferreira, R. J., Garcia, C., Monteiro, C. M., Dinić, J., Holmstedt, S., André, V., Pešić, M., Dos Santos, D. J. V. A., Candeias, N. R., Afonso, C. A. M.,& Rijo, P.. (2020). Molecular Docking Studies of Royleanone Diterpenoids from Plectranthus spp. as P-Glycoprotein Inhibitors. in ACS Medicinal Chemistry Letters
Washington : ACS Publications., 11(5), 839-845.
https://doi.org/10.1021/acsmedchemlett.9b00642

Isca VMS, Ferreira RJ, Garcia C, Monteiro CM, Dinić J, Holmstedt S, André V, Pešić M, Dos Santos DJVA, Candeias NR, Afonso CAM, Rijo P. Molecular Docking Studies of Royleanone Diterpenoids from Plectranthus spp. as P-Glycoprotein Inhibitors. in ACS Medicinal Chemistry Letters. 2020;11(5):839-845.
doi:10.1021/acsmedchemlett.9b00642 .

Isca, Vera M. S., Ferreira, Ricardo J., Garcia, Catarina, Monteiro, Carlos M., Dinić, Jelena, Holmstedt, Suvi, André, Vânia, Pešić, Milica, Dos Santos, Daniel J. V. A., Candeias, Nuno R., Afonso, Carlos A. M., Rijo, Patrícia, "Molecular Docking Studies of Royleanone Diterpenoids from Plectranthus spp. as P-Glycoprotein Inhibitors" in ACS Medicinal Chemistry Letters, 11, no. 5 (2020):839-845,
https://doi.org/10.1021/acsmedchemlett.9b00642 . .

TY  - JOUR
AU  - Isca, Vera M. S.
AU  - Ferreira, Ricardo J.
AU  - Garcia, Catarina
AU  - Monteiro, Carlos M.
AU  - Dinić, Jelena
AU  - Holmstedt, Suvi
AU  - André, Vânia
AU  - Pešić, Milica
AU  - Dos Santos, Daniel J. V. A.
AU  - Candeias, Nuno R.
AU  - Afonso, Carlos A. M.
AU  - Rijo, Patrícia
PY  - 2020
UR  - https://pubs.acs.org/doi/10.1021/acsmedchemlett.9b00642
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3817
AB  - The development of multidrug resistance (MDR) is a major cause of failure in cancer chemotherapy. Several abietane diterpenes with antitumoral activities have been isolated from Plectranthus spp. such as 6,7-dehydroroyleanone (DHR, 1) and 7α-acetoxy-6β-hydroxyroyleanone (AHR, 2). Several royleanone derivatives were prepared through hemisynthesis from natural compounds 1 and 2 to achieve a small library of products with enhanced anti-P-glycoprotein activity. Nonetheless, some derivatives tend to be unstable. Therefore, to reason such lack of stability, the electron density based local reactivity descriptors condensed Fukui functions and dual descriptor were calculated for several derivatives of DHR. Additionally, molecular docking and molecular dynamics studies were performed on several other derivatives to clarify the molecular mechanisms by which they may exert their inhibitory effect in P-gp activity. The analysis on local reactivity descriptors was important to understand possible degradation pathways and to guide further synthetic approaches toward new royleanone derivatives. A molecular docking study suggested that the presence of aromatic moieties increases the binding affinity of royleanone derivatives toward P-gp. It further suggests that one royleanone benzoylated derivative may act as a noncompetitive efflux modulator when bound to the M-site. The future generation of novel royleanone derivatives will involve (i) a selective modification of position C-12 with chemical moieties smaller than unsubstituted benzoyl rings and (ii) the modification of the substitution pattern of the benzoyloxy moiety at position C-6.
PB  - Washington : ACS Publications
T2  - ACS Medicinal Chemistry Letters
T1  - Molecular Docking Studies of Royleanone Diterpenoids from Plectranthus spp. as P-Glycoprotein Inhibitors
IS  - 5
VL  - 11
DO  - 10.1021/acsmedchemlett.9b00642
SP  - 839
EP  - 845
ER  - 

@article{
author = "Isca, Vera M. S. and Ferreira, Ricardo J. and Garcia, Catarina and Monteiro, Carlos M. and Dinić, Jelena and Holmstedt, Suvi and André, Vânia and Pešić, Milica and Dos Santos, Daniel J. V. A. and Candeias, Nuno R. and Afonso, Carlos A. M. and Rijo, Patrícia",
year = "2020",
abstract = "The development of multidrug resistance (MDR) is a major cause of failure in cancer chemotherapy. Several abietane diterpenes with antitumoral activities have been isolated from Plectranthus spp. such as 6,7-dehydroroyleanone (DHR, 1) and 7α-acetoxy-6β-hydroxyroyleanone (AHR, 2). Several royleanone derivatives were prepared through hemisynthesis from natural compounds 1 and 2 to achieve a small library of products with enhanced anti-P-glycoprotein activity. Nonetheless, some derivatives tend to be unstable. Therefore, to reason such lack of stability, the electron density based local reactivity descriptors condensed Fukui functions and dual descriptor were calculated for several derivatives of DHR. Additionally, molecular docking and molecular dynamics studies were performed on several other derivatives to clarify the molecular mechanisms by which they may exert their inhibitory effect in P-gp activity. The analysis on local reactivity descriptors was important to understand possible degradation pathways and to guide further synthetic approaches toward new royleanone derivatives. A molecular docking study suggested that the presence of aromatic moieties increases the binding affinity of royleanone derivatives toward P-gp. It further suggests that one royleanone benzoylated derivative may act as a noncompetitive efflux modulator when bound to the M-site. The future generation of novel royleanone derivatives will involve (i) a selective modification of position C-12 with chemical moieties smaller than unsubstituted benzoyl rings and (ii) the modification of the substitution pattern of the benzoyloxy moiety at position C-6.",
publisher = "Washington : ACS Publications",
journal = "ACS Medicinal Chemistry Letters",
title = "Molecular Docking Studies of Royleanone Diterpenoids from Plectranthus spp. as P-Glycoprotein Inhibitors",
number = "5",
volume = "11",
doi = "10.1021/acsmedchemlett.9b00642",
pages = "839-845"
}

Isca, V. M. S., Ferreira, R. J., Garcia, C., Monteiro, C. M., Dinić, J., Holmstedt, S., André, V., Pešić, M., Dos Santos, D. J. V. A., Candeias, N. R., Afonso, C. A. M.,& Rijo, P.. (2020). Molecular Docking Studies of Royleanone Diterpenoids from Plectranthus spp. as P-Glycoprotein Inhibitors. in ACS Medicinal Chemistry Letters
Washington : ACS Publications., 11(5), 839-845.
https://doi.org/10.1021/acsmedchemlett.9b00642

Isca VMS, Ferreira RJ, Garcia C, Monteiro CM, Dinić J, Holmstedt S, André V, Pešić M, Dos Santos DJVA, Candeias NR, Afonso CAM, Rijo P. Molecular Docking Studies of Royleanone Diterpenoids from Plectranthus spp. as P-Glycoprotein Inhibitors. in ACS Medicinal Chemistry Letters. 2020;11(5):839-845.
doi:10.1021/acsmedchemlett.9b00642 .

Isca, Vera M. S., Ferreira, Ricardo J., Garcia, Catarina, Monteiro, Carlos M., Dinić, Jelena, Holmstedt, Suvi, André, Vânia, Pešić, Milica, Dos Santos, Daniel J. V. A., Candeias, Nuno R., Afonso, Carlos A. M., Rijo, Patrícia, "Molecular Docking Studies of Royleanone Diterpenoids from Plectranthus spp. as P-Glycoprotein Inhibitors" in ACS Medicinal Chemistry Letters, 11, no. 5 (2020):839-845,
https://doi.org/10.1021/acsmedchemlett.9b00642 . .

TY  - JOUR
AU  - Garcia, Catarina
AU  - Ntungwe, Epole
AU  - Rebelo, Ana
AU  - Bessa, Cláudia
AU  - Stanković, Tijana
AU  - Dinić, Jelena
AU  - Díaz-Lanza, Ana
AU  - P Reis, Catarina
AU  - Roberto, Amílcar
AU  - Pereira, Paula
AU  - Cebola, Maria-João
AU  - Saraiva, Lucília
AU  - Pešić, Milica
AU  - Duarte, Noélia
AU  - Rijo, Patrícia
PY  - 2019
UR  - https://www.mdpi.com/2218-273X/9/10/616
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3492
AB  - The Plectranthus genus is commonly used in traditional medicine due to its potential to treat several illnesses, including bacterial infections and cancer. As such, aiming to screen the antibacterial and cytotoxic activities of extracts, sixteen selected Plectranthus species with medicinal potential were studied. In total, 31 extracts obtained from 16 Plectranthus spp. were tested for their antibacterial and anticancer properties. Well diffusion method was used for preliminary antibacterial screening. The minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values of the five most active acetonic extracts (P. aliciae, P. japonicus, P. madagascariensis var. "Lynne", P. stylesii, and P. strigosus) were determined. After preliminary toxicity evaluation on Artemia salina L., their cytotoxic properties were assessed on three human cancer cell lines (HCT116, MCF-7, and H460). These were also selected for mechanism of resistance studies (on NCI-H460/R and DLD1-TxR cells). An identified compound-parvifloron D-was tested in a pair of sensitive and MDR-Multidrug resistance cancer cells (NCI-H460 and NCI-H460/R) and in normal bronchial fibroblasts MRC-5. The chemical composition of the most active extract was studied through high performance liquid chromatography with a diode array detector (HPLC-DAD/UV) and liquid chromatography-mass spectrometry (LC-MS). Overall, P. strigosus acetonic extract showed the strongest antimicrobial and cytotoxic potential that could be explained by the presence of parvifloron D, a highly cytotoxic diterpene. This study provides valuable information on the use of the Plectranthus genus as a source of bioactive compounds, namely P. strigosus with the potential active ingredient the parvifloron D.
T2  - Biomolecules
T1  - Parvifloron D from Plectranthusstrigosus: Cytotoxicity Screening of Plectranthus spp. Extracts.
IS  - 10
VL  - 9
DO  - 10.3390/biom9100616
SP  - 616
ER  - 

@article{
author = "Garcia, Catarina and Ntungwe, Epole and Rebelo, Ana and Bessa, Cláudia and Stanković, Tijana and Dinić, Jelena and Díaz-Lanza, Ana and P Reis, Catarina and Roberto, Amílcar and Pereira, Paula and Cebola, Maria-João and Saraiva, Lucília and Pešić, Milica and Duarte, Noélia and Rijo, Patrícia",
year = "2019",
abstract = "The Plectranthus genus is commonly used in traditional medicine due to its potential to treat several illnesses, including bacterial infections and cancer. As such, aiming to screen the antibacterial and cytotoxic activities of extracts, sixteen selected Plectranthus species with medicinal potential were studied. In total, 31 extracts obtained from 16 Plectranthus spp. were tested for their antibacterial and anticancer properties. Well diffusion method was used for preliminary antibacterial screening. The minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values of the five most active acetonic extracts (P. aliciae, P. japonicus, P. madagascariensis var. "Lynne", P. stylesii, and P. strigosus) were determined. After preliminary toxicity evaluation on Artemia salina L., their cytotoxic properties were assessed on three human cancer cell lines (HCT116, MCF-7, and H460). These were also selected for mechanism of resistance studies (on NCI-H460/R and DLD1-TxR cells). An identified compound-parvifloron D-was tested in a pair of sensitive and MDR-Multidrug resistance cancer cells (NCI-H460 and NCI-H460/R) and in normal bronchial fibroblasts MRC-5. The chemical composition of the most active extract was studied through high performance liquid chromatography with a diode array detector (HPLC-DAD/UV) and liquid chromatography-mass spectrometry (LC-MS). Overall, P. strigosus acetonic extract showed the strongest antimicrobial and cytotoxic potential that could be explained by the presence of parvifloron D, a highly cytotoxic diterpene. This study provides valuable information on the use of the Plectranthus genus as a source of bioactive compounds, namely P. strigosus with the potential active ingredient the parvifloron D.",
journal = "Biomolecules",
title = "Parvifloron D from Plectranthusstrigosus: Cytotoxicity Screening of Plectranthus spp. Extracts.",
number = "10",
volume = "9",
doi = "10.3390/biom9100616",
pages = "616"
}

Garcia, C., Ntungwe, E., Rebelo, A., Bessa, C., Stanković, T., Dinić, J., Díaz-Lanza, A., P Reis, C., Roberto, A., Pereira, P., Cebola, M., Saraiva, L., Pešić, M., Duarte, N.,& Rijo, P.. (2019). Parvifloron D from Plectranthusstrigosus: Cytotoxicity Screening of Plectranthus spp. Extracts.. in Biomolecules, 9(10), 616.
https://doi.org/10.3390/biom9100616

Garcia C, Ntungwe E, Rebelo A, Bessa C, Stanković T, Dinić J, Díaz-Lanza A, P Reis C, Roberto A, Pereira P, Cebola M, Saraiva L, Pešić M, Duarte N, Rijo P. Parvifloron D from Plectranthusstrigosus: Cytotoxicity Screening of Plectranthus spp. Extracts.. in Biomolecules. 2019;9(10):616.
doi:10.3390/biom9100616 .

Garcia, Catarina, Ntungwe, Epole, Rebelo, Ana, Bessa, Cláudia, Stanković, Tijana, Dinić, Jelena, Díaz-Lanza, Ana, P Reis, Catarina, Roberto, Amílcar, Pereira, Paula, Cebola, Maria-João, Saraiva, Lucília, Pešić, Milica, Duarte, Noélia, Rijo, Patrícia, "Parvifloron D from Plectranthusstrigosus: Cytotoxicity Screening of Plectranthus spp. Extracts." in Biomolecules, 9, no. 10 (2019):616,
https://doi.org/10.3390/biom9100616 . .

TY  - JOUR
AU  - Matias, Diogo
AU  - Nicolai, Marisa
AU  - Saraiva, Lucília
AU  - Pinheiro, Rute
AU  - Faustino, Célia
AU  - Diaz Lanza, Ana
AU  - Pinto Reis, Catarina
AU  - Stanković, Tijana
AU  - Dinić, Jelena
AU  - Pešić, Milica
AU  - Rijo, Patrícia
PY  - 2019
UR  - http://pubs.acs.org/doi/10.1021/acsomega.9b00512
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3349
AB  - Cytotoxicity screenings have identified Plectranthus plants as potential sources of antitumor lead compounds. In this work, several extracts from Plectranthus madagascariensis were prepared using different solvents (acetone, methanol, and supercritical CO2) and extraction techniques (maceration, ultrasound-assisted, and supercritical fluid extraction), and their chemical composition was detailed using high-performance liquid chromatography with a diode array detector. The cytotoxic activity of the major compounds identified, namely, rosmarinic acid (1) and abietane diterpenes 7α,6β-dihydroxyroyleanone (2), 7α-formyloxy-6β-hydroxyroyleanone (3), 7α-acetoxy-6β-hydroxyroyleanone (4), and coleon U (5), was evaluated in a battery of human cancer cell lines, including breast (MDA-MB-231, MCF-7), colon (HCT116), and lung (NCI-H460, NCI-H460/R) cancer, and also in healthy lung (MCR-5) cells. Royleanone (3) was isolated for the first time from P. madagascariensis, and its full spectroscopic characterization (proto...
T2  - ACS Omega
T1  - Cytotoxic Activity of Royleanone Diterpenes from <i>Plectranthus madagascariensis</i> Benth
IS  - 5
VL  - 4
DO  - 10.1021/acsomega.9b00512
SP  - 8094
EP  - 8103
ER  - 

@article{
author = "Matias, Diogo and Nicolai, Marisa and Saraiva, Lucília and Pinheiro, Rute and Faustino, Célia and Diaz Lanza, Ana and Pinto Reis, Catarina and Stanković, Tijana and Dinić, Jelena and Pešić, Milica and Rijo, Patrícia",
year = "2019",
abstract = "Cytotoxicity screenings have identified Plectranthus plants as potential sources of antitumor lead compounds. In this work, several extracts from Plectranthus madagascariensis were prepared using different solvents (acetone, methanol, and supercritical CO2) and extraction techniques (maceration, ultrasound-assisted, and supercritical fluid extraction), and their chemical composition was detailed using high-performance liquid chromatography with a diode array detector. The cytotoxic activity of the major compounds identified, namely, rosmarinic acid (1) and abietane diterpenes 7α,6β-dihydroxyroyleanone (2), 7α-formyloxy-6β-hydroxyroyleanone (3), 7α-acetoxy-6β-hydroxyroyleanone (4), and coleon U (5), was evaluated in a battery of human cancer cell lines, including breast (MDA-MB-231, MCF-7), colon (HCT116), and lung (NCI-H460, NCI-H460/R) cancer, and also in healthy lung (MCR-5) cells. Royleanone (3) was isolated for the first time from P. madagascariensis, and its full spectroscopic characterization (proto...",
journal = "ACS Omega",
title = "Cytotoxic Activity of Royleanone Diterpenes from <i>Plectranthus madagascariensis</i> Benth",
number = "5",
volume = "4",
doi = "10.1021/acsomega.9b00512",
pages = "8094-8103"
}

Matias, D., Nicolai, M., Saraiva, L., Pinheiro, R., Faustino, C., Diaz Lanza, A., Pinto Reis, C., Stanković, T., Dinić, J., Pešić, M.,& Rijo, P.. (2019). Cytotoxic Activity of Royleanone Diterpenes from <i>Plectranthus madagascariensis</i> Benth. in ACS Omega, 4(5), 8094-8103.
https://doi.org/10.1021/acsomega.9b00512

Matias D, Nicolai M, Saraiva L, Pinheiro R, Faustino C, Diaz Lanza A, Pinto Reis C, Stanković T, Dinić J, Pešić M, Rijo P. Cytotoxic Activity of Royleanone Diterpenes from <i>Plectranthus madagascariensis</i> Benth. in ACS Omega. 2019;4(5):8094-8103.
doi:10.1021/acsomega.9b00512 .

Matias, Diogo, Nicolai, Marisa, Saraiva, Lucília, Pinheiro, Rute, Faustino, Célia, Diaz Lanza, Ana, Pinto Reis, Catarina, Stanković, Tijana, Dinić, Jelena, Pešić, Milica, Rijo, Patrícia, "Cytotoxic Activity of Royleanone Diterpenes from <i>Plectranthus madagascariensis</i> Benth" in ACS Omega, 4, no. 5 (2019):8094-8103,
https://doi.org/10.1021/acsomega.9b00512 . .

TY  - JOUR
AU  - Garcia, Catarina
AU  - Silva, Catarina Oliveira
AU  - Monteiro, Carlos M
AU  - Nicolai, Marisa
AU  - Viana, Ana
AU  - Andrade, Joana M
AU  - Barasoain, Isabel
AU  - Stanković, Tijana
AU  - Quintana, José
AU  - Hernández, Inmaculada
AU  - González, Ignacio
AU  - Estévez, Francisco
AU  - Díaz-Lanza, Ana M
AU  - Reis, Catarina P
AU  - Afonso, Carlos AM
AU  - Pešić, Milica
AU  - Rijo, Patrícia
PY  - 2018
UR  - https://www.future-science.com/doi/10.4155/fmc-2017-0239
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3086
AB  - AIM 6,7-dehydroroyleanone (DHR) is a cytotoxic abietane present in the essential oil of Plectranthus madagascariensis. METHODS/RESULTS Different extraction parameters were tested, and its extraction optimization was accomplished with a Clevenger apparatus-based hydrodistillation. After isolation, its effect on microtubules, P-glycoprotein and caspases was assessed on several cell lines and the compound was coupled with hybrid nanoparticles. The results show that DHR does not interfere with microtubule formation, but evades the resistance mechanisms of P-glycoprotein. Strong activation of caspases-3 and -9 indicates that DHR is able to induce apoptosis by triggering the intrinsic cell death pathway. Moreover, the assembly of DHR with hybrid nanoparticles was able to potentiate the effect of DHR in cancer cells. CONCLUSION DHR seems to be a promising starting material with anticancer properties to further be explored.
T2  - Future Medicinal Chemistry
T1  - Anticancer properties of the abietane diterpene 6,7-dehydroroyleanone obtained by optimized extraction.
IS  - 10
VL  - 10
DO  - 10.4155/fmc-2017-0239
SP  - 1177
EP  - 1189
ER  - 

@article{
author = "Garcia, Catarina and Silva, Catarina Oliveira and Monteiro, Carlos M and Nicolai, Marisa and Viana, Ana and Andrade, Joana M and Barasoain, Isabel and Stanković, Tijana and Quintana, José and Hernández, Inmaculada and González, Ignacio and Estévez, Francisco and Díaz-Lanza, Ana M and Reis, Catarina P and Afonso, Carlos AM and Pešić, Milica and Rijo, Patrícia",
year = "2018",
abstract = "AIM 6,7-dehydroroyleanone (DHR) is a cytotoxic abietane present in the essential oil of Plectranthus madagascariensis. METHODS/RESULTS Different extraction parameters were tested, and its extraction optimization was accomplished with a Clevenger apparatus-based hydrodistillation. After isolation, its effect on microtubules, P-glycoprotein and caspases was assessed on several cell lines and the compound was coupled with hybrid nanoparticles. The results show that DHR does not interfere with microtubule formation, but evades the resistance mechanisms of P-glycoprotein. Strong activation of caspases-3 and -9 indicates that DHR is able to induce apoptosis by triggering the intrinsic cell death pathway. Moreover, the assembly of DHR with hybrid nanoparticles was able to potentiate the effect of DHR in cancer cells. CONCLUSION DHR seems to be a promising starting material with anticancer properties to further be explored.",
journal = "Future Medicinal Chemistry",
title = "Anticancer properties of the abietane diterpene 6,7-dehydroroyleanone obtained by optimized extraction.",
number = "10",
volume = "10",
doi = "10.4155/fmc-2017-0239",
pages = "1177-1189"
}

Garcia, C., Silva, C. O., Monteiro, C. M., Nicolai, M., Viana, A., Andrade, J. M., Barasoain, I., Stanković, T., Quintana, J., Hernández, I., González, I., Estévez, F., Díaz-Lanza, A. M., Reis, C. P., Afonso, C. A., Pešić, M.,& Rijo, P.. (2018). Anticancer properties of the abietane diterpene 6,7-dehydroroyleanone obtained by optimized extraction.. in Future Medicinal Chemistry, 10(10), 1177-1189.
https://doi.org/10.4155/fmc-2017-0239

Garcia C, Silva CO, Monteiro CM, Nicolai M, Viana A, Andrade JM, Barasoain I, Stanković T, Quintana J, Hernández I, González I, Estévez F, Díaz-Lanza AM, Reis CP, Afonso CA, Pešić M, Rijo P. Anticancer properties of the abietane diterpene 6,7-dehydroroyleanone obtained by optimized extraction.. in Future Medicinal Chemistry. 2018;10(10):1177-1189.
doi:10.4155/fmc-2017-0239 .

Garcia, Catarina, Silva, Catarina Oliveira, Monteiro, Carlos M, Nicolai, Marisa, Viana, Ana, Andrade, Joana M, Barasoain, Isabel, Stanković, Tijana, Quintana, José, Hernández, Inmaculada, González, Ignacio, Estévez, Francisco, Díaz-Lanza, Ana M, Reis, Catarina P, Afonso, Carlos AM, Pešić, Milica, Rijo, Patrícia, "Anticancer properties of the abietane diterpene 6,7-dehydroroyleanone obtained by optimized extraction." in Future Medicinal Chemistry, 10, no. 10 (2018):1177-1189,
https://doi.org/10.4155/fmc-2017-0239 . .