SYNTHESIS, CHARACTERIZATION AND ANTITUMOR-ACTIVITY OF PLATINUM TRIAMINE COMPLEXES CONTAINING IMIDAZOTHIAZOLE LIGANDS

A series of platinum(II) and platinum(IV) triamine complexes was prepa red, characterized and evaluated as potential antitumor agents. The co mplexes 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, NH3, or A(2) is the bidentate amine, ethylenediamine (en), and N-het is an imidazo thiazole or a derivative. The structures of two of the platinum comple xes, [Pt(en)(C5H6N2OS)Cl]NO3 (5b) and [Pt(en)(C5H6N2OS)Cl-3]NO3 (5e), were determined by single-crystal X-ray diffraction. Crystals of compl ex 5b were orthorhombic in space group Pna2(1), a=9.2451(7), b=18.950( 2), c=7.908(2) Angstrom, Z=4. Those of complex 5e were triclinic in sp ace group P(-1), a=8.2884(9), b=10.853(1), c=11.244(2) Angstrom, alpha =72.50(1), beta=70.42(1), gamma=67.905(9)degrees, Z=2. Biological acti vity was measured by in vitro assay against S180, L1210 and L1210/DDP cell lines, and IC50 values were calculated by linear regression analy sis 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 cytot oxicity in vitro. Furthermore, this work shows that cytotoxic complexe s were not restricted to compounds with planar ligands, in contrast to previous reports. Platinum(IV) derivatives were as active or more act ive than their Pt(II) analogues.