Molecular drug design, synthesis and crystal structure determination of CuII-SnIV heterobimetallic core: DNA binding and cleavage studies

A novel heterobimetallic Cu-II-Sn-IV complex 1 bearing bioactive 1,10-phenanthroline pharmacophore ligand scaffold was synthesized and characterized by elemental analysis, IR, UV-vis spectroscopy, Mass (ESI and FAB) and X-ray crystallography. The in vitro DNA binding studies of complex 1 with CT DNA was carried out by various biophysical and molecular docking techniques which revealed that complex 1 binds to DNA through intercalation in the minor groove having AT-rich sequences. Complex 1 exhibits high chemical nuclease activity cleaving supercoiled pBR322 DNA via hydrolytic pathway which was further evidenced by T4 DNA ligase assay. The complex 1 shows high inhibitory activity against Topo I at a very low concentration (15 mu M), suggesting that complex 1 is an efficient catalytic inhibitor of human Topo I and further validated by molecular docking studies. (C) 2012 Elsevier Masson SAS. All rights reserved.