Mixed-ligand Cu(II)–vanillin Schiff base complexes; effect of coligands on their DNA binding, DNA cleavage, SOD mimetic and anticancer activity

SOD mimics with varying coligand are momentous in developing potential chemotherapeutic drugs. Cu(II) based SOD mimics 1–4 [CuLH(OAc)(H2O)Y)] (LH = 2-((E)-(1,3-dihydroxy-2-methylpropan-2-ylimino)methyl)-6-methoxyphenol, OAc = CH3COO, 1: Y = H2O; 2: Y = phen (1,10-phenanthroline), 3: Y = tpimH (2,4,5-triphenylimidazole); 4: Y = tfbimH (2-(trifluoromethyl)benzimidazole) were synthesized and thoroughly characterized. Their interaction with CT-DNA showed different non-covalent binding behaviour. SOD activity of 2 was highest among 1–4 which was further validated by gel electrophoresis. The pBR322 plasmid strand break offered by 2 + O2·−O2·− system reveals oxidative cleavage mechanism. In vitro antimicrobial activity of 1–4 was shown by percent inhibition data while in vitro anticancer activity of 1–4 was screened using 16 human carcinoma cell lines of different histological origin. Complex 2 showed higher efficacy towards 14 cell lines.

Graphical abstractNitrogen-donar-bridged Cu(II) binding site with distorted square pyramidal geometry are absolutely essential for SOD activity. Oxidation by O2·−O2·− to give H2O2 is a proton-coupled electron transfer followed by outer or inner sphere pathway.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► 1–4 exhibit novel structure because of active sites that mimics native SOD enzyme. ► Complexes with free –OH pertains to guanidinium group of Arg residue of native SOD. ► Nitrogen containing heterocyclic units act as substitute for His residues. ► Distorted structure around Cu(II) is feasible for the attack of O2·−O2·−.