TY  - CONF
AU  - Isca, Vera
AU  - Ntungwe, Epole
AU  - Bangay, Gabrielle
AU  - Princiotto, Salvatore
AU  - Dinić, Jelena
AU  - Pešić, Milica
AU  - Saraiva, Lucilia
AU  - Afonso, Carlos
AU  - Rijo, Patricia
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5611
AB  - Natural products are an important source of lead compounds for drug discovery. Plectranthus (Lamiaceae family) is an Old-World genus widely used in traditional medicine, whose species are rich in pharmacologically active compounds, specifically diterpenes. Two important lead molecules reported in Plectranthus spp. are the diterpenoids 7α-acetoxy-6β-hydroxyroyleanone (Roy, [Fig. 1]) and 6,7-dehydroroyleanone (DeRoy, [Fig. 1]) [1]. Previous studies reported in vitro activity of Roy and DeRoy against several breast cancer cell lines [1], [2]. Furthermore, in silico studies suggested promising interactions of these natural royleanones with protein kinase C (PKC) isoforms [2]. The key point of this work was to prepare new functionalized derivatives of Roy and DeRoy and evaluate their effect on two cancer targets, PKC isoforms and the efflux pump, P-glycoprotein (P-gp). New royleanone derivatives were obtained by hemi-synthesis, starting from Roy and DeRoy. Some of these compounds were evaluated as PKC (α, βI, δ, ε and ζ) activators. One benzoylated analogue showed the ability to selectively activate PKC-δ, while DeRoy displayed improved PKC activity, compared with the positive control, in all tested isoforms. Additionally, P-gp inhibitory potential was evaluated in human non-small cell lung carcinoma NCI-H460 and its MDR counterpart NCI-H460/R. Natural royleanones Roy and DeRoy showed similar cytotoxic activity against both NCI-H460 and MDR cancer cell lines. Interestingly, the benzoylated derivatives displayed the most promising results, showing an increased P-gp inhibitory activity and suggesting a relevant role of this moiety for the cytotoxic activity. Several other derivatives are currently under investigation as potential chemotherapeutic agents.
PB  - Thieme Medical Publishers
C3  - 70th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA); 2022 Aug 28-31; Thessaloniki, Greece
T1  - Natural and semi-synthetic royleanone diterpenoids from Plectranthus spp. as potential anti-tumoral agents
DO  - 10.1055/s-0042-1759260
SP  - 1540
ER  - 

@conference{
author = "Isca, Vera and Ntungwe, Epole and Bangay, Gabrielle and Princiotto, Salvatore and Dinić, Jelena and Pešić, Milica and Saraiva, Lucilia and Afonso, Carlos and Rijo, Patricia",
year = "2022",
abstract = "Natural products are an important source of lead compounds for drug discovery. Plectranthus (Lamiaceae family) is an Old-World genus widely used in traditional medicine, whose species are rich in pharmacologically active compounds, specifically diterpenes. Two important lead molecules reported in Plectranthus spp. are the diterpenoids 7α-acetoxy-6β-hydroxyroyleanone (Roy, [Fig. 1]) and 6,7-dehydroroyleanone (DeRoy, [Fig. 1]) [1]. Previous studies reported in vitro activity of Roy and DeRoy against several breast cancer cell lines [1], [2]. Furthermore, in silico studies suggested promising interactions of these natural royleanones with protein kinase C (PKC) isoforms [2]. The key point of this work was to prepare new functionalized derivatives of Roy and DeRoy and evaluate their effect on two cancer targets, PKC isoforms and the efflux pump, P-glycoprotein (P-gp). New royleanone derivatives were obtained by hemi-synthesis, starting from Roy and DeRoy. Some of these compounds were evaluated as PKC (α, βI, δ, ε and ζ) activators. One benzoylated analogue showed the ability to selectively activate PKC-δ, while DeRoy displayed improved PKC activity, compared with the positive control, in all tested isoforms. Additionally, P-gp inhibitory potential was evaluated in human non-small cell lung carcinoma NCI-H460 and its MDR counterpart NCI-H460/R. Natural royleanones Roy and DeRoy showed similar cytotoxic activity against both NCI-H460 and MDR cancer cell lines. Interestingly, the benzoylated derivatives displayed the most promising results, showing an increased P-gp inhibitory activity and suggesting a relevant role of this moiety for the cytotoxic activity. Several other derivatives are currently under investigation as potential chemotherapeutic agents.",
publisher = "Thieme Medical Publishers",
journal = "70th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA); 2022 Aug 28-31; Thessaloniki, Greece",
title = "Natural and semi-synthetic royleanone diterpenoids from Plectranthus spp. as potential anti-tumoral agents",
doi = "10.1055/s-0042-1759260",
pages = "1540"
}

Isca, V., Ntungwe, E., Bangay, G., Princiotto, S., Dinić, J., Pešić, M., Saraiva, L., Afonso, C.,& Rijo, P.. (2022). Natural and semi-synthetic royleanone diterpenoids from Plectranthus spp. as potential anti-tumoral agents. in 70th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA); 2022 Aug 28-31; Thessaloniki, Greece
Thieme Medical Publishers., 1540.
https://doi.org/10.1055/s-0042-1759260

Isca V, Ntungwe E, Bangay G, Princiotto S, Dinić J, Pešić M, Saraiva L, Afonso C, Rijo P. Natural and semi-synthetic royleanone diterpenoids from Plectranthus spp. as potential anti-tumoral agents. in 70th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA); 2022 Aug 28-31; Thessaloniki, Greece. 2022;:1540.
doi:10.1055/s-0042-1759260 .

Isca, Vera, Ntungwe, Epole, Bangay, Gabrielle, Princiotto, Salvatore, Dinić, Jelena, Pešić, Milica, Saraiva, Lucilia, Afonso, Carlos, Rijo, Patricia, "Natural and semi-synthetic royleanone diterpenoids from Plectranthus spp. as potential anti-tumoral agents" in 70th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA); 2022 Aug 28-31; Thessaloniki, Greece (2022):1540,
https://doi.org/10.1055/s-0042-1759260 . .

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  - CONF
AU  - Isca, Vera
AU  - Coelho, Jaime
AU  - Monteiro, Carlos
AU  - Ntungwe, Epole
AU  - Dominguez-Martin, Eva Maria
AU  - Dinić, Jelena
AU  - Diaz-Lanza, Ana Maria
AU  - Candeias, Nuno R.
AU  - Afonso, Carlos A.M.
AU  - Pešić, Milica
AU  - Rijo, Patricia
PY  - 2020
UR  - https://stratagem-cost.eu/wp-content/uploads/2020/11/Abstract-Book-WG3-meeting-Nov-2020.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5624
AB  - Multidrug resistance (MDR) is one of the main challenges in cancer treatment, in which overexpression of
P-glycoprotein (P-gp) plays an important role. Therefore, there is an urgent need to identify new
compounds that can exert anticancer effects and at the same time revert MDR. In this context, Plectranthus
genus (Lamiaceae) is a great source of cytotoxic compounds that could be used as lead molecules for
drug development, such as 6,7-dehydroroyleanone (1) (P. madagascariensis (Pers.) Benth. essential oil)
and 7α-acetoxy-6β-hydroxyroyleanone (2) (P. grandidentatus Gürke) [1].
The aim of this work was to prepare a small library of new 12-O-substituted derivatives with potential P-gp
inhibitory effect by exploring the reactivity of the natural royleanones 1 and 2. In this study, we identified a
new derivative that exhibited a P-gp inhibitory activity higher than the natural diterpenes 1 and 2, and
comparable to Dexverapamil. Furthermore, this compound showed the ability to sensitize the resistant cell
line NCI-H460/R to doxorubicin. This activity was evaluated in the human non-small cell lung carcinoma
(NCI-H460) cell line and its MDR counterpart NCI-H460/R with the P-gp overexpression by using the MTT
and Rhodamine 123 accumulation assays. Further derivatizations and quantitative structure–activity
relationship analysis are ongoing to discover new derivatives with improved activity.

References: [1] Isca VMS et al. (2020). ACS Med Chem Lett. 11 (5): 839-845
PB  - COST Action CA17104
C3  - Abstract book: COST Action 17104 (STRATAGEM) WG3 Meeting - International Online Symposium on “New Therapeutic Tools Against Preclinical Models of Multidrug Resistant Tumors”; 2020 Nov 4; Online.
T1  - Novel class of P-glycoprotein inhibitors from Plectranthus spp.
SP  - 30
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5624
ER  - 

@conference{
author = "Isca, Vera and Coelho, Jaime and Monteiro, Carlos and Ntungwe, Epole and Dominguez-Martin, Eva Maria and Dinić, Jelena and Diaz-Lanza, Ana Maria and Candeias, Nuno R. and Afonso, Carlos A.M. and Pešić, Milica and Rijo, Patricia",
year = "2020",
abstract = "Multidrug resistance (MDR) is one of the main challenges in cancer treatment, in which overexpression of
P-glycoprotein (P-gp) plays an important role. Therefore, there is an urgent need to identify new
compounds that can exert anticancer effects and at the same time revert MDR. In this context, Plectranthus
genus (Lamiaceae) is a great source of cytotoxic compounds that could be used as lead molecules for
drug development, such as 6,7-dehydroroyleanone (1) (P. madagascariensis (Pers.) Benth. essential oil)
and 7α-acetoxy-6β-hydroxyroyleanone (2) (P. grandidentatus Gürke) [1].
The aim of this work was to prepare a small library of new 12-O-substituted derivatives with potential P-gp
inhibitory effect by exploring the reactivity of the natural royleanones 1 and 2. In this study, we identified a
new derivative that exhibited a P-gp inhibitory activity higher than the natural diterpenes 1 and 2, and
comparable to Dexverapamil. Furthermore, this compound showed the ability to sensitize the resistant cell
line NCI-H460/R to doxorubicin. This activity was evaluated in the human non-small cell lung carcinoma
(NCI-H460) cell line and its MDR counterpart NCI-H460/R with the P-gp overexpression by using the MTT
and Rhodamine 123 accumulation assays. Further derivatizations and quantitative structure–activity
relationship analysis are ongoing to discover new derivatives with improved activity.

References: [1] Isca VMS et al. (2020). ACS Med Chem Lett. 11 (5): 839-845",
publisher = "COST Action CA17104",
journal = "Abstract book: COST Action 17104 (STRATAGEM) WG3 Meeting - International Online Symposium on “New Therapeutic Tools Against Preclinical Models of Multidrug Resistant Tumors”; 2020 Nov 4; Online.",
title = "Novel class of P-glycoprotein inhibitors from Plectranthus spp.",
pages = "30",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5624"
}

Isca, V., Coelho, J., Monteiro, C., Ntungwe, E., Dominguez-Martin, E. M., Dinić, J., Diaz-Lanza, A. M., Candeias, N. R., Afonso, C. A.M., Pešić, M.,& Rijo, P.. (2020). Novel class of P-glycoprotein inhibitors from Plectranthus spp.. in Abstract book: COST Action 17104 (STRATAGEM) WG3 Meeting - International Online Symposium on “New Therapeutic Tools Against Preclinical Models of Multidrug Resistant Tumors”; 2020 Nov 4; Online.
COST Action CA17104., 30.
https://hdl.handle.net/21.15107/rcub_ibiss_5624

Isca V, Coelho J, Monteiro C, Ntungwe E, Dominguez-Martin EM, Dinić J, Diaz-Lanza AM, Candeias NR, Afonso CA, Pešić M, Rijo P. Novel class of P-glycoprotein inhibitors from Plectranthus spp.. in Abstract book: COST Action 17104 (STRATAGEM) WG3 Meeting - International Online Symposium on “New Therapeutic Tools Against Preclinical Models of Multidrug Resistant Tumors”; 2020 Nov 4; Online.. 2020;:30.
https://hdl.handle.net/21.15107/rcub_ibiss_5624 .

Isca, Vera, Coelho, Jaime, Monteiro, Carlos, Ntungwe, Epole, Dominguez-Martin, Eva Maria, Dinić, Jelena, Diaz-Lanza, Ana Maria, Candeias, Nuno R., Afonso, Carlos A.M., Pešić, Milica, Rijo, Patricia, "Novel class of P-glycoprotein inhibitors from Plectranthus spp." in Abstract book: COST Action 17104 (STRATAGEM) WG3 Meeting - International Online Symposium on “New Therapeutic Tools Against Preclinical Models of Multidrug Resistant Tumors”; 2020 Nov 4; Online. (2020):30,
https://hdl.handle.net/21.15107/rcub_ibiss_5624 .

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  - 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 . .