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 . .

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 . .