<abstract xmlns="http://www.w3.org/1999/xhtml">Twelve previously synthesized, biologically active 2,6,7-trihydroxyxanthen-3-one derivatives were evaluated <italic>in vitro</italic> for antiproliferative activity. Compounds were screened against HeLa, SW620, HepG2 and A549 tumor cell lines. Compound with the trifluormethyl group on C-4’ position of the phenyl ring showed the best inhibitory activity towards HeLa and A549 tumor cells with <italic>IC</italic>50 of 0.7 and 4.1 µmol L−1, resp. Compound with chlorine and fluorine substituents on aryl ring showed the best antiproliferative activity against SW620 with <italic>IC</italic>50 of 4.1 µmol L–1 and against HepG2 tumor cell line with <italic>IC</italic>50 of 4.2 µmol L–1. Analyses of cytotoxic and genotoxic potential of the trifluormethyl derivative were performed with cytokinesis-block micronucleus cytome assay in human lymphocyte culture and revealed no genotoxic and cytotoxic effects. The most potent compounds were subjected to molecular docking simulations in order to analyse bindings to molecular targets and, at the same time, further support the results of experimental cytotoxic tests. Docking studies showed sites of importance in forming hydrogen bonds of the most potent compounds with targets of interest.</abstract>

Twelve previously synthesized, biologically active 2,6,7-trihydroxyxanthen-3-one derivatives were evaluated in vitro for antiproliferative activity. Compounds were screened against HeLa, SW620, HepG2 and A549 tumor cell lines. Compound with the trifluormethyl group on C-4’ position of the phenyl ring showed the best inhibitory activity towards HeLa and A549 tumor cells with IC50 of 0.7 and 4.1 µmol L−1, resp. Compound with chlorine and fluorine substituents on aryl ring showed the best antiproliferative activity against SW620 with IC50 of 4.1 µmol L–1 and against HepG2 tumor cell line with IC50 of 4.2 µmol L–1. Analyses of cytotoxic and genotoxic potential of the trifluormethyl derivative were performed with cytokinesis-block micronucleus cytome assay in human lymphocyte culture and revealed no genotoxic and cytotoxic effects. The most potent compounds were subjected to molecular docking simulations in order to analyse bindings to molecular targets and, at the same time, further support the results of experimental cytotoxic tests. Docking studies showed sites of importance in forming hydrogen bonds of the most potent compounds with targets of interest.

Antiproliferative and genotoxic potential of xanthen-3-one derivatives

Institute for Genetic Engineering and Biotechnology

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

{"article-title":"Antiproliferative and genotoxic potential of xanthen-3-one derivatives"}

Twelve previously synthesized, biologically active 2,6,7-trihydroxyxanthen-3-one derivatives were evaluated in vitro for antiproliferative activity. Compounds...

Antiproliferative and genotoxic potential of xanthen-3-one derivatives

Published Online: Oct 21, 2019

Page range: 683 - 694

Accepted: May 10, 2019

DOI: https://doi.org/10.2478/acph-2019-0044

Keywords
antiproliferative activity, genotoxic potential, docking study, xanthen-3-one derivatives, cytokinesis-block micronucleus cytome assay

© 2019 Elma Veljović et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Antiproliferative and genotoxic potential of xanthen-3-one derivatives

Published Online: Oct 21, 2019

Page range: 683 - 694

Accepted: May 10, 2019

DOI: https://doi.org/10.2478/acph-2019-0044

Keywordsantiproliferative activity, genotoxic potential, docking study, xanthen-3-one derivatives, cytokinesis-block micronucleus cytome assay

© 2019 Elma Veljović et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
antiproliferative activity, genotoxic potential, docking study, xanthen-3-one derivatives, cytokinesis-block micronucleus cytome assay