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  - CONF
AU  - Nešović, Marija
AU  - Garcia, Catarina
AU  - Stanković, Tijana
AU  - Dinić, Jelena
AU  - Podolski-Renić, Ana
AU  - Stojkovic Burić, Sonja
AU  - Dragoj, Miodrag
AU  - Jovanović, Mirna
AU  - Rijo, Patricia
AU  - Pešić, Milica
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6434
AB  - The genus Plectranthus has been widely used in traditional medicine to treat numerous diseases, including cancer. In this study, 31 extracts obtained from 16 Plectranthus spp. with medicinal potential were evaluated for their anticancer properties. The cytotoxic effects of all extracts were assessed in non-small cell lung carcinoma cell line NCI-H460. Five most promising Plectranthus spp. extracts (P. aliciae, P. japonicus, P. malvinus, P. stylesii and P. strigosus) were additionally tested for growth inhibition activity in multidrug resistant (MDR) cell lines with P-glycoprotein overexpression: NCI-H460/R (non-small cell lung carcinoma) and DLD1-TxR (colorectal adenocarcinoma), and compared to their sensitive counterparts, NCI-H460 and DLD1. P. strigosus acetonic extract was shown to be the most active. Parvifloron D, a diterpene identified in this extract, was tested in NCI-H460 and NCI-H460/R cells, as well as normal human embryonic bronchial fibroblasts (MRC-5) to evaluate its selectivity against cancer cells. It displayed the same efficacy in sensitive and MDR cancer cells, implying that parvifloron D is not a substrate for P-glycoprotein. Flow-cytometric analysis revealed that while parvifloron D is not exported via the P glycoprotein, it does not possess the potential to inhibit this transporter’s activity in NCI-H460/R cells. This study provides valuable information on the use of the Plectranthus genus as a source of therapeutically useful compounds against cancer cells including those with MDR phenotype, as well as compounds potentially responsible for their activity such as abietane diterpene parvifloron D. Additionally, the bioactivities of several Plectranthus spp. not previously described are reported.
PB  - Belgrade: Serbian Plant Physiology Society
C3  - Book of abstracts. 3rd International Conference on Plant Biology (22nd SPPS Meeting); 2018 Jun 9-12; Belgrade, Serbia
T1  - Evaluation of anticancer activity of Plectranthus spp. extracts
SP  - 149
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6434
ER  - 

@conference{
author = "Nešović, Marija and Garcia, Catarina and Stanković, Tijana and Dinić, Jelena and Podolski-Renić, Ana and Stojkovic Burić, Sonja and Dragoj, Miodrag and Jovanović, Mirna and Rijo, Patricia and Pešić, Milica",
year = "2018",
abstract = "The genus Plectranthus has been widely used in traditional medicine to treat numerous diseases, including cancer. In this study, 31 extracts obtained from 16 Plectranthus spp. with medicinal potential were evaluated for their anticancer properties. The cytotoxic effects of all extracts were assessed in non-small cell lung carcinoma cell line NCI-H460. Five most promising Plectranthus spp. extracts (P. aliciae, P. japonicus, P. malvinus, P. stylesii and P. strigosus) were additionally tested for growth inhibition activity in multidrug resistant (MDR) cell lines with P-glycoprotein overexpression: NCI-H460/R (non-small cell lung carcinoma) and DLD1-TxR (colorectal adenocarcinoma), and compared to their sensitive counterparts, NCI-H460 and DLD1. P. strigosus acetonic extract was shown to be the most active. Parvifloron D, a diterpene identified in this extract, was tested in NCI-H460 and NCI-H460/R cells, as well as normal human embryonic bronchial fibroblasts (MRC-5) to evaluate its selectivity against cancer cells. It displayed the same efficacy in sensitive and MDR cancer cells, implying that parvifloron D is not a substrate for P-glycoprotein. Flow-cytometric analysis revealed that while parvifloron D is not exported via the P glycoprotein, it does not possess the potential to inhibit this transporter’s activity in NCI-H460/R cells. This study provides valuable information on the use of the Plectranthus genus as a source of therapeutically useful compounds against cancer cells including those with MDR phenotype, as well as compounds potentially responsible for their activity such as abietane diterpene parvifloron D. Additionally, the bioactivities of several Plectranthus spp. not previously described are reported.",
publisher = "Belgrade: Serbian Plant Physiology Society",
journal = "Book of abstracts. 3rd International Conference on Plant Biology (22nd SPPS Meeting); 2018 Jun 9-12; Belgrade, Serbia",
title = "Evaluation of anticancer activity of Plectranthus spp. extracts",
pages = "149",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6434"
}

Nešović, M., Garcia, C., Stanković, T., Dinić, J., Podolski-Renić, A., Stojkovic Burić, S., Dragoj, M., Jovanović, M., Rijo, P.,& Pešić, M.. (2018). Evaluation of anticancer activity of Plectranthus spp. extracts. in Book of abstracts. 3rd International Conference on Plant Biology (22nd SPPS Meeting); 2018 Jun 9-12; Belgrade, Serbia
Belgrade: Serbian Plant Physiology Society., 149.
https://hdl.handle.net/21.15107/rcub_ibiss_6434

Nešović M, Garcia C, Stanković T, Dinić J, Podolski-Renić A, Stojkovic Burić S, Dragoj M, Jovanović M, Rijo P, Pešić M. Evaluation of anticancer activity of Plectranthus spp. extracts. in Book of abstracts. 3rd International Conference on Plant Biology (22nd SPPS Meeting); 2018 Jun 9-12; Belgrade, Serbia. 2018;:149.
https://hdl.handle.net/21.15107/rcub_ibiss_6434 .

Nešović, Marija, Garcia, Catarina, Stanković, Tijana, Dinić, Jelena, Podolski-Renić, Ana, Stojkovic Burić, Sonja, Dragoj, Miodrag, Jovanović, Mirna, Rijo, Patricia, Pešić, Milica, "Evaluation of anticancer activity of Plectranthus spp. extracts" in Book of abstracts. 3rd International Conference on Plant Biology (22nd SPPS Meeting); 2018 Jun 9-12; Belgrade, Serbia (2018):149,
https://hdl.handle.net/21.15107/rcub_ibiss_6434 .

TY  - CONF
AU  - Nešović, Marija
AU  - Garcia, Catarina
AU  - Stanković, Tijana
AU  - Dinić, Jelena
AU  - Podolski-Renić, Ana
AU  - Stojković Burić, Sonja
AU  - Dragoj, Miodrag
AU  - Jovanović, Mirna
AU  - Rijo, Patricia
AU  - Pešić, Milica
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6433
AB  - Natural compound-based green chemistry has been the focus of current nanobiotechnology
research to improve efficacy and safety of medicines through targeted drug delivery. The Lamiaceae family, widely used in traditional medicine, is a well-known source of natural compounds with
anticancer properties. A wide spectrum of bioactive diterpenes have been isolated from the genus Plectranthus, including 6,7-dehydroroyleanone (DHR), a abietane found in the essential oil of P.
madagascariensis. The biological activity of DHR was investigated in P-glycoprotein-overexpressing multidrug resistant (MDR) non-small cell lung cancer cell line (NCI-H460/R), its sensitive counterpart (NCI-H460) and normal human embryonic bronchial epithelial cells (MRC-5). DHR showed
significant growth inhibition and slight selectivity against cancer cell lines when compared to
normal cells. The results also confirmed that DHR is not a substrate for P-glycoprotein as it does
not interfere with its activity. This diterpene was incorporated into Hybrid nanoparticles in order
to increase treatment efficacy and delivery selectivity. Anticancer properties of this nanosystem
were compared to the activity of DHR alone. Additionally, to address the problem of multidrug
resistance, this nanosystem was tested against cancer cells with MDR phenotype. Coupling of
DHR with Hybrid nanoparticles additionally improved the cytotoxicity of DHR, decreasing the IC50
value 8-fold in NCI-H460 cells and 5-fold in NCI-H460/R cells. These findings imply that combining
natural products, such as DHR, with nanoparticles could be considered as a promising anticancer
strategy with potential to overcome drug resistance.
PB  - Belgrade: Serbian Plant Physiology Society; Institute for Biological Research "Siniša Stanković"; Faculty of Biology
C3  - Book of abstracts. 3rd International Conference on Plant Biology (22nd SPPS Meeting); 2018 Jun 9-12; Belgrade, Serbia
T1  - Anticancer properties of the abietane diterpene 6,7-dehydroroyleanone from Plectranthus madagascariensis
SP  - 150
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6433
ER  - 

@conference{
author = "Nešović, Marija and Garcia, Catarina and Stanković, Tijana and Dinić, Jelena and Podolski-Renić, Ana and Stojković Burić, Sonja and Dragoj, Miodrag and Jovanović, Mirna and Rijo, Patricia and Pešić, Milica",
year = "2018",
abstract = "Natural compound-based green chemistry has been the focus of current nanobiotechnology
research to improve efficacy and safety of medicines through targeted drug delivery. The Lamiaceae family, widely used in traditional medicine, is a well-known source of natural compounds with
anticancer properties. A wide spectrum of bioactive diterpenes have been isolated from the genus Plectranthus, including 6,7-dehydroroyleanone (DHR), a abietane found in the essential oil of P.
madagascariensis. The biological activity of DHR was investigated in P-glycoprotein-overexpressing multidrug resistant (MDR) non-small cell lung cancer cell line (NCI-H460/R), its sensitive counterpart (NCI-H460) and normal human embryonic bronchial epithelial cells (MRC-5). DHR showed
significant growth inhibition and slight selectivity against cancer cell lines when compared to
normal cells. The results also confirmed that DHR is not a substrate for P-glycoprotein as it does
not interfere with its activity. This diterpene was incorporated into Hybrid nanoparticles in order
to increase treatment efficacy and delivery selectivity. Anticancer properties of this nanosystem
were compared to the activity of DHR alone. Additionally, to address the problem of multidrug
resistance, this nanosystem was tested against cancer cells with MDR phenotype. Coupling of
DHR with Hybrid nanoparticles additionally improved the cytotoxicity of DHR, decreasing the IC50
value 8-fold in NCI-H460 cells and 5-fold in NCI-H460/R cells. These findings imply that combining
natural products, such as DHR, with nanoparticles could be considered as a promising anticancer
strategy with potential to overcome drug resistance.",
publisher = "Belgrade: Serbian Plant Physiology Society; Institute for Biological Research "Siniša Stanković"; Faculty of Biology",
journal = "Book of abstracts. 3rd International Conference on Plant Biology (22nd SPPS Meeting); 2018 Jun 9-12; Belgrade, Serbia",
title = "Anticancer properties of the abietane diterpene 6,7-dehydroroyleanone from Plectranthus madagascariensis",
pages = "150",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6433"
}

Nešović, M., Garcia, C., Stanković, T., Dinić, J., Podolski-Renić, A., Stojković Burić, S., Dragoj, M., Jovanović, M., Rijo, P.,& Pešić, M.. (2018). Anticancer properties of the abietane diterpene 6,7-dehydroroyleanone from Plectranthus madagascariensis. in Book of abstracts. 3rd International Conference on Plant Biology (22nd SPPS Meeting); 2018 Jun 9-12; Belgrade, Serbia
Belgrade: Serbian Plant Physiology Society; Institute for Biological Research "Siniša Stanković"; Faculty of Biology., 150.
https://hdl.handle.net/21.15107/rcub_ibiss_6433

Nešović M, Garcia C, Stanković T, Dinić J, Podolski-Renić A, Stojković Burić S, Dragoj M, Jovanović M, Rijo P, Pešić M. Anticancer properties of the abietane diterpene 6,7-dehydroroyleanone from Plectranthus madagascariensis. in Book of abstracts. 3rd International Conference on Plant Biology (22nd SPPS Meeting); 2018 Jun 9-12; Belgrade, Serbia. 2018;:150.
https://hdl.handle.net/21.15107/rcub_ibiss_6433 .

Nešović, Marija, Garcia, Catarina, Stanković, Tijana, Dinić, Jelena, Podolski-Renić, Ana, Stojković Burić, Sonja, Dragoj, Miodrag, Jovanović, Mirna, Rijo, Patricia, Pešić, Milica, "Anticancer properties of the abietane diterpene 6,7-dehydroroyleanone from Plectranthus madagascariensis" in Book of abstracts. 3rd International Conference on Plant Biology (22nd SPPS Meeting); 2018 Jun 9-12; Belgrade, Serbia (2018):150,
https://hdl.handle.net/21.15107/rcub_ibiss_6433 .

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 . .