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 .