Synthesis, characterization and antitumor activity of platinum triamine complexes containing imidazothiazole ligands

Abstract A series of platinum(II) and platinum(IV) triamine complexes was prepared, characterized and evaluated as potential antitumor agents. The complexes were cis or trans isomers of the form [PtA 2 (N-het)Cl] + or [PtA 2 (N-het)Cl 3 ] + , where A is the monodentate amine, NH 3 , or A 2 is the bidentate amine, ethylenediamine (en), and N-het is an imidazothiazole or a derivative. The structures of two of the platinum complexes, [Pt(en)(C 5 H 6 N 2 OS)Cl]NO 3 ( 5b ) and [Pt(en)(C 5 H 6 N 2 OS)Cl 3 ]NO 3 ( 5e ), were determined by single-crystal X-ray diffraction. Crystals of complex 5b were orthorhombic in space group Pna2 1 , a = 9.2451(7), b = 18.950(2), c = 7.908(2) A , Z = 4 . Those of complex 5e were triclinic in space group P(−1), a = 8.2884(9), b = 10.853(1), c = 11.244(2) A , α = 72.50(1), β = 70.42(1), Z = 2 . Biological activity was measured by in vitro assay against S180, L1210 and L1210/DDP cell lines, and IC 50 values were calculated by linear regression analysis of the data. Results from these preliminary screens indicate that compounds having cis ammine groups are more active than those with the trans arrangement, consistent with prior observations. Complexes with ligands derived from benzimidazole moieties displayed promising cytotoxicity in vitro. Furthermore, this work shows that cytotoxic complexes were not restricted to compounds with planar ligands, in contrast to previous reports. Platinum(IV) derivatives were as active or more active than their Pt(II) analogues.