Acta Pharm. 69 (2019) 683-694

 

full paper

Original research paper

 

Antiproliferative and genotoxic potential of xanthen-3-one derivatives

ELMA VELJOVIĆ, SELMA ŠPIRTOVIĆ-HALILOVIĆ, SAMIJA MURATOVIĆ, AMAR OSMANOVIĆ, SANIN HAVERIĆ, ANJA HAVERIĆ, MAIDA HADŽIĆ, MIRSADA SALIHOVIĆ, MAJA MALENICA, AIDA ŠAPČANIN and DAVORKA ZAVRŠNIK

elma.veljovic@ffsa.unsa.ba

1 University of Sarajevo- Faculty of Pharmacy, 71000 Sarajevo, Bosnia and Herzegovina

2 University of Sarajevo- Institute for Genetic Engineering and Biotechnology, 71000 Sarajevo, Bosnia and Herzegovina

Accepted May 10, 2019

Published online July 5, 2019

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 µmol L–1 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.

 

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