New modulated design, docking and synthesis of carbohydrate-conjugate heterobimetallic Cu~II-Sn~IV complex as potential topoisomerase II inhibitor: In vitro DNA binding, cleavage and cytotoxicity against human cancer cell lines

摘要

New carbohydrate-conjugate heterobimetallic complexes [C_(22)H_(50)N_6O_(13)CuSnCl_2] (3) and [C_(22)H_(58)N_6O_(17)-] NiSnCl_2] (4) were synthesized from their monometallic analogs [C_(22)H_(52)N_6O_(13)Cu)] (1) and [C_(22)H_(60)N_6O_(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.