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

Abstract

Organochalcogen (S/Se) functionalized chrysin derivatives were synthesized and coordinated with Ru^II(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 (K_b) 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

Graphical Abstract

Keywords:

• organochalcogen
• Ru^II(η⁶-p-cymene) complexes
• DNA/HSA interaction
• in vitro cytotoxicity
• molecular docking

Acknowledgements

The authors gratefully acknowledge Prof. Yoshiaki Nishibayashi, University of Tokyo, Japan for his valuable inputs in accomplishing this work. The authors are thankful to Department of Chemistry, IIT Delhi for instrumentation facility and Anti-Cancer Drug Screening Facility (ACDSF) at ACTREC, Mumbai for carrying out the in vitro anticancer activity.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The author S. Yadav thanks Science & Engineering Research Board (SERB) a statutory body of the Department of Science & Technology (DST) for the financial support under project grant PDF/2016/002767.