Abstract
New metal-based anticancer chemotherapeutic drug candidates [Cu(phen)L](NO3)(2) (1) and [Zn(phen)L](NO3)(2) (2) were synthesized from ligand L (derived from pharmacophore scaffold barbituric acid and pyrazole). In vitro DNA binding studies of the L, 1 and 2 were carried out by various biophysical techniques revealing electrostatic mode. Complex 1 cleaves pBR322 DNA via oxidative pathway and recognizes major groove of DNA double helix. The molecular docking study was carried out to ascertain the mode of action towards the molecular target DNA and enzymes. The complex 1 exhibited remarkably good anticancer activity on a panel of human cancer cell lines (GI(50) values < 10 mu g/ml), and to elucidate the mechanism of cancer inhibition, Topo-I enzymatic activity was carried out. (C) 2014 Elsevier Masson SAS. All rights reserved.