TY  - JOUR
AU  - Isca, Vera M.S.
AU  - Sencanski, Milan
AU  - Filipović, Nenad
AU  - Dos Santos, Daniel J.V.A.
AU  - Cipak-Gasparović, Ana
AU  - Saraiva, Lucilia
AU  - Afonso, Carlos A.M.
AU  - Rijo, Patricia
AU  - Garcia-Sosa, Alfonso T.
PY  - 2020
UR  - http://aspace.agrif.bg.ac.rs/handle/123456789/5386
AB  - Plants have been used for centuries to treat several illnesses. The Plectranthus genus has a vast variety of species that has allowed the isolation of cytotoxic compounds with notable activities. The abietane diterpenes 6,7-dehydroroyleanone (DeRoy, 1), 7 alpha -acetoxy-6 beta -hydroxyroyleanone (Roy, 2), and Parvifloron D (ParvD, 3) were obtained from Plectranthus spp. and showed promising biological activities, such as cytotoxicity. The inhibitory effects of the different natural abietanes (1-3) were compared in MFC7, SkBr3, and SUM159 cell lines, as well as SUM159 grown in cancer stem cell-inducing conditions. Based on the royleanones' bioactivity, the derivatives RoyBz (4), RoyBzCl (5), RoyPr(2) (6), and DihydroxyRoy (7), previously obtained from 2, were selected for further studies. Protein kinases C (PKCs) are involved in several carcinogenic processes. Thus, PKCs are potential targets for cancer therapy. To date, the portfolio of available PKC modulators remains very limited due to the difficulty of designing isozyme-selective PKC modulators. As such, molecular docking was used to evaluate royleanones 1-6 as predicted isozyme-selective PKC binders. Subtle changes in the binding site of each PKC isoform change the predicted interaction profiles of the ligands. Subtle changes in royleanone substitution patterns, such as a double substitution only with non-substituted phenyls, or hydroxybenzoate at position four that flips the binding mode of ParvD (3), can increase the predicted interactions in certain PKC subtypes.
PB  - MDPI, BASEL
T2  - International Journal of Molecular Sciences
T1  - Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones
IS  - 10
VL  - 21
DO  - 10.3390/ijms21103671
ER  - 

@article{
author = "Isca, Vera M.S. and Sencanski, Milan and Filipović, Nenad and Dos Santos, Daniel J.V.A. and Cipak-Gasparović, Ana and Saraiva, Lucilia and Afonso, Carlos A.M. and Rijo, Patricia and Garcia-Sosa, Alfonso T.",
year = "2020",
abstract = "Plants have been used for centuries to treat several illnesses. The Plectranthus genus has a vast variety of species that has allowed the isolation of cytotoxic compounds with notable activities. The abietane diterpenes 6,7-dehydroroyleanone (DeRoy, 1), 7 alpha -acetoxy-6 beta -hydroxyroyleanone (Roy, 2), and Parvifloron D (ParvD, 3) were obtained from Plectranthus spp. and showed promising biological activities, such as cytotoxicity. The inhibitory effects of the different natural abietanes (1-3) were compared in MFC7, SkBr3, and SUM159 cell lines, as well as SUM159 grown in cancer stem cell-inducing conditions. Based on the royleanones' bioactivity, the derivatives RoyBz (4), RoyBzCl (5), RoyPr(2) (6), and DihydroxyRoy (7), previously obtained from 2, were selected for further studies. Protein kinases C (PKCs) are involved in several carcinogenic processes. Thus, PKCs are potential targets for cancer therapy. To date, the portfolio of available PKC modulators remains very limited due to the difficulty of designing isozyme-selective PKC modulators. As such, molecular docking was used to evaluate royleanones 1-6 as predicted isozyme-selective PKC binders. Subtle changes in the binding site of each PKC isoform change the predicted interaction profiles of the ligands. Subtle changes in royleanone substitution patterns, such as a double substitution only with non-substituted phenyls, or hydroxybenzoate at position four that flips the binding mode of ParvD (3), can increase the predicted interactions in certain PKC subtypes.",
publisher = "MDPI, BASEL",
journal = "International Journal of Molecular Sciences",
title = "Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones",
number = "10",
volume = "21",
doi = "10.3390/ijms21103671"
}

Isca, V. M.S., Sencanski, M., Filipović, N., Dos Santos, D. J.V.A., Cipak-Gasparović, A., Saraiva, L., Afonso, C. A.M., Rijo, P.,& Garcia-Sosa, A. T.. (2020). Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones. in International Journal of Molecular Sciences
MDPI, BASEL., 21(10).
https://doi.org/10.3390/ijms21103671

Isca VM, Sencanski M, Filipović N, Dos Santos DJ, Cipak-Gasparović A, Saraiva L, Afonso CA, Rijo P, Garcia-Sosa AT. Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones. in International Journal of Molecular Sciences. 2020;21(10).
doi:10.3390/ijms21103671 .

Isca, Vera M.S., Sencanski, Milan, Filipović, Nenad, Dos Santos, Daniel J.V.A., Cipak-Gasparović, Ana, Saraiva, Lucilia, Afonso, Carlos A.M., Rijo, Patricia, Garcia-Sosa, Alfonso T., "Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones" in International Journal of Molecular Sciences, 21, no. 10 (2020),
https://doi.org/10.3390/ijms21103671 . .