Synthesis, characterization, DNA binding, topoisomerase I inhibition and antiproliferation activities of three new functionalized terpyridine platinum(II) complexes

Abstract Three new platinum(II) complexes with pendent morpholine were synthesized, namely complex 1 ([Pt(L)Cl]CF 3 SO 3 ), complex 2 ([Pt(L)(NH 3 )](CF 3 SO 3 ) 2 ) and complex 3 ([Pt(L)(PPh 3 )](CF 3 SO 3 ) 2 ), where L = 4′-[4-(4-morpholinobutyloxy)phenyl]-2,2′:6′,2″-terpyridine and PPh 3  = triphenylphosphine. The detailed molecular structures of complex 3 , L and its precursor L′ (1,4′-[4-(4-bromobutyloxy)phenyl]-2,2′:6′,2″-terpyridine) were determined by single crystal X-ray diffraction. An evaluation of in vitro cytotoxicity for both ligand and complexes was performed by methyl thiazolyl tetrazolium (MTT) assay in three cancer cell lines and normal cells as the control, respectively. IC 50 values of complexes 1 – 3 were lower than those exhibited for the reference drug cisplatin, and selectivity of these complexes were greater than cisplatin. Among them, complex 3 with a leaving group PPh 3 was found to be the most efficacious complex against certain cell lines, especially for cisplatin-resistant A549cisR cells. These complexes were found to bind DNA, induce efficient DNA unwinding. Meanwhile, topoisomerase (Topo) I inhibitory activities by three complexes were detected, and a minimum inhibitory concentration of 15 μM of complex 3 was found totally inhibit Topo I activity.