Synthesis and preliminary biological evaluation for the anticancer activity of organochalcogen (S/se) tethered chrysin-based organometallic RuII(η6-p-cymene) complexes

Abstract

Organochalcogen (S/Se) functionalized chrysin derivatives were synthesized and coordinated with RuII(η6-p-cymene) to efficiently form ruthenium-based chemotherapeutic drug entities [C31H35O4SRuCl]; [C31H35O4SeRuCl]; [C33H31O4SRuCl]; and [C33H31O4SeRuCl]. The complexes were thoroughly characterized by analytical and various spectroscopic techniques which include elemental analysis, UV–vis, IR, NMR (1H, 13C, and 77Se NMR), and HR-MS. The interaction studies of these Ru(II) complexes were carried out with CT DNA/HSA by employing UV–vis, fluorescence and circular dichroic techniques in view to examine their chemotherapeutic potential. The complexes demonstrated predominant binding toward CTDNA via electrostatic interaction while, the extent of binding was quantified by calculating intrinsic binding constant (Kb) and binding constant (K) values which revealed higher binding affinity of selenium-based chrysin complexes as compared to their thio-analogs, following the order [C31H35O4SeRuCl] > [C33H31O4SeRuCl] > [C31H35O4SRuCl] > [C33H31O4SRuCl]. Moreover, interaction of these complexes with human serum albumin (HSA) was also investigated which suggested spontaneous interactions of complexes with the protein by hydrogen bonding and van der Waals forces. To visualize the preferential binding sites and affinity of complexes with DNA and HSA molecular docking studies were performed. Additionally, in vitro anticancer activity of the complexes were evaluated by SRB assay on selected cancer cell lines viz., HeLa (cervical), MIA-PA-CA-2 (pancreatic), MCF-7 (breast), Hep-G2 (Hepatoma), and SK-OV-3 (ovarian) which exhibited the superior cytotoxicity of complex [C31H35O4SeRuCl] as compared to other analogs on selective cancer phenotypes.Communicated by Ramaswamy H. Sarma