CYTOTOXIC ANIONIC TRIBROMO PLATINUM(II) COMPLEXES CONTAINING BENZOTHIAZOLE AND BENZOXAZOLE DONORS - SYNTHESIS, CHARACTERIZATION, AND STRUCTURE-ACTIVITY CORRELATION

A series of platinum(II) complexes of the type [NEt4][PtLBr3] where L is a 2-styrylbenzothiazole or 2-styrylbenzoxazole was prepared. The co mplexes were characterized by their melting points, elemental analyses , W-Vis and far-infrared spectra, and H-1 and Pt-195 NMR spectroscopy. The NMR data are consistent with coordination of the benzoheterazole ligands to the Pt ion through the nitrogen atom. The ligands and the c omplexes were assayed for cytotoxicity against U937 human histiocytic lymphoma cells. It was observed that the ligands displayed very poor c ytotoxicity, while the Pt(II) complexes demonstrated marked cytotoxici ties and a structure-activity correlation was established. Pt(ll) comp lexes containing S as the heteroatom in the benzoheterazole ring were generally more active than their O-containing counterpart. The positio n and type of substituents in the styryl moiety were also important fo r biological activity. Our data indicate that adjacent methoxy functio nalities were present in the most potent drugs tested. Further develop ment of active Pt(II) complexes with improved solubilities is warrante d. (C) 1998 Elsevier Science S.A.