Acta Pharm. 69 (2019) 683-694
Short communication
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
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