In-vitro and in-silico analysis and antitumor studies of novel Cu(II) and V(V) complexes of N-p-Tolylbenzohydroxamic acid

Abstract

Copper(L₂Cu) and vanadium(L₂VOCl) complexes of N-p-tolylbenzohydroxamic acid (LH) ligand have been investigated for DNA binding efficacy by multiple analytical, spectral, and computational techniques. The results revealed that complexes as groove binders as evidenced by UV absorption. Fluorescence studies including displacement assay using classical intercalator ethidium bromide as fluorescent probe also confirmed as groove binders. The viscometric analysis too supports the inferences as strong groove binders for both the complexes. Molecular docking too exposed DNA as a target to the complexes which precisely binds L₂Cu, in the minor groove region while L₂VOCl in major groove region. Molecular dynamic simulation performed on L₂Cu complex revealing the interaction of complex with DNA within 20 ns time. The complex stacked into the nitrogen bases of oligonucleotides and the bonding features were intrinsically preserved for longer simulation times. In-vitro cytotoxicity study was undertaken employing MTT assay against the breast cancer cell line (MCF-7). Potential cytotoxic activities were observed for L₂Cu and L₂VOCl complexes with IC₅₀ values of showing 71 % and 74 % of inhibition respectively.

Keywords: Computational analysis; Fluorescence studies; In vitro cytotoxic activity; Metal complexes.