The chiral monometallic Cu(II) (1) and Zn(II) (2) and heterobimetallic Cu(II)-Sn(IV) and Zn(II)-Sn(IV) complexes with tridentate chiral Schiff base -ONO-ligand in the presence of nitrogen donor heterocyclic ligand imidazole; were prepared and characterized by various physico-chemical and spectroscopic methods. Preliminary complex-DNA interaction studies employing optical methods revealed that 3 displayed a higher propensity towards the drug target DNA double helix and recommended predominantly an electrostatic mode of interaction as well as a groove binding affinity of the complex with CT-DNA. This was quantified by Kb and KSV values of complexes 1-4, which demonstrated a multifold increase in complex 3 binding to CT DNA and clearly demonstrates its potency to act as a chemotherapeutic agent. Furthermore, the gel electrophoretic patterns of supercoiled pBR322 DNA with varying concentrations of complex 3 exhibits the ability to cleave DNA and follow a freely diffusible radical mechanism. The antiproliferative effects of complex 3 on human hepatoma cancer cells (Huh7) was investigated. Human Topo I inhibition assay by complex 3 was performed and results confirmed significantly good activity at lower concentrations than some of the classical Topo I inhibitors. Additionally, complex 3 was investigated for the expression of MMP-2 and TGF-β by real time PCR. The cellular uptake of complex 3 by HeLa cells was studied by confocal microscopy.
New chiral l-valine-derived Schiff base complexes with the bioactive heterocyclic ligand scaffold pyrazole (Hpz) were designed and synthesized with a view to find their potential as anticancer chemotherapeutic drug candidates.
The chloro-bridged heterobimetallic complex (η 6hexamethylbenzene)Ru(dmp)(μ-Cl) 2 Sn(CH 3 ) 2 Cl 2 was designed, synthesized, and characterized by various spectroscopic methods, viz. IR, 1 H and 13 C NMR, and ESI MS, and single-crystal X-ray crystallography as an approach toward multitargeting metal-based potential anticancer drug candidates. In vitro DNA binding studies confirmed the binding affinity of the complex toward the minor groove of DNA, which is further validated by docking studies. Furthermore, the complex exhibited significant inhibitory effects on topoisomerase Iα at a very low concentration (∼8 μM). The cytotoxicity of the complex against HeLa and HepG2 cancer cell lines was evaluated, which revealed significant regression in cancerous cells in comparison with the standard drug.
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