Design and synthesis of new Zn(II) nalidixic acid-DACH based Topo-II inhibiting molecular entity: Chemotherapeutic potential validated by its in vitro binding profile, pBR322 cleavage activity and molecular docking studies with DNA and RNA molecular targets

Abstract

Nalidixic acid-DACH based Zn(II) molecular entity (1) was synthesized and thoroughly characterized by spectroscopic techniques (FT-IR, 1H and 13C NMR, ESI-MS) and single crystal X-ray crystallography as a potential chemotherapeutic drug candidate. The comparative in vitro binding studies of complex 1 with targets like CT-DNA and yeast tRNA were carried out by employing UV-Vis, emission spectroscopy, circular dichroism and viscosity which revealed higher binding affinity of 1 towards yeast tRNA as compared to CT-DNA. Complex 1 cleaves pBR322 plasmid via hydrolytic pathway (validated by T4 religation assay); in addition, 1 also exhibited significant inhibitory effects on the catalytic activity of Topo-II at a concentration of 30 μM. Further, validation of the interaction studies was accomplished by carrying out molecular docking studies with DNA, RNA and Topo-II targets. This work also advances our knowledge for the development and design of small RNA targeted therapeutic molecules which were relatively under exploited drug targets. © 2014 Elsevier B.V. All rights reserved.