Abstract
New carbohydrate-conjugate heterobimetallic complexes [C22H50N6O13CuSnCl2] (3) and [C(22)H(58)N(6)0(17)NiSnCl(2)] (4) were synthesized from their monometallic analogs [C(22)H(52)N(6)0(13)Cu] (1) and [C(22)H(60)N(6)0(17)Ni] (2) containing N-glycoside ligand (L). In vitro DNA binding studies of L and complexes (1 4) with CT DNA were carried out by employing various biophysical and molecular docking techniques which revealed that heterobimetallic complex 3 strongly binds to DNA in comparison to 4, monometallic complexes (1 and 2) and the free ligand. Complex 3 cleaves pBR322 DNA via hydrolytic pathway (confirmed by T4 DNA ligase assay) and inhibited Topo-II activity in a dose-dependent manner. Furthermore, complex 3 was docked into the ATPase domain of human-Topo-II in order to probe the possible mechanism of inhibition. (C) 2013 Elsevier Masson SAS. All rights reserved.