Abstract
A new water soluble (2,2′–bipyridine)–(phenylalaninato)–μ–chlorido–copper(II) complex was synthesized using ancillary ligands, l-phenylalanine, and 2,2-bipyridine as a chemotherapeutic anticancer agent. The complex was characterized by employing various spectroscopic (UV–visible, FT-IR, EPR, elemental analysis) and single crystal X-ray diffraction technique which revealed the structure of crystal as monoclinic with P21 space group. The interaction studies of the complex with therapeutic drug target, ct-DNA were caried out using various complimentary biophysical techniques, and the corroborative results of these experiments revealed that complex binds avidly through non-covalent electrostatic binding mode in the groove region of DNA. The binding propensity was quantified by calculating the intrinsic binding constant values (Kb and Ksv) which were found to be 3.1 (±0.95) × 105M−1 and 0.4 (±0.05) × 103M−1, respectively. The cleavage studies of copper(II) based drug candidate 1 with pBR322 plasmid DNA were performed in concentration dependent manner and it was demonstrated that complex was capable of conversion of supercoiled form SC (Form I) into nicked form NC (Form II) upon incubation of 3 μM concentration, implicating efficient single strand cleavage of DNA helix. The mechanistic cleavage studies were also performed in the presence various activators viz., DMSO, NaN3, SOD, and H2O2 and the strong inhibition of cleavage process was observed in presence of NaN3 and SOD that suggested an oxidative pathway (Fenton's mechanism) for the Cu(II) complex. The cytotoxicity of the complex was evaluated by SRB assay against the resistant cancer cell lines, viz., Hop-62, MCF-7, AW13516, MDA-MB-231, and SiHa. The cytotoxicity activity demonstrated good therapeutic potency against all the tested cell lines with GI50 value of <10 μM.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call