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  - 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  - 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 . .