COORDINATION CHEMISTRY OF TROPOLONE-BASED ANTIMITOTIC DRUGS AND THE ANTINEOPLASTIC BEHAVIOR OF SOME RUTHENIUM(II) AND PLATINUM(II) DERIVATIVES

Aspects of the coordination chemistry of the antimitotics colchicine ( Col) and trimethylcolchicinic acid (Tmca) with the metal fragments Pt( bpy)(2+) and Ru(bpy)(2)(2+) are reported. In addition, the coordinatio n chemistry of the tropolone anion (Tp) with the same fragments, which serves as a model for one mode of binding of the antimitotic, is desc ribed. The new complexes have been characterized by a variety of spect roscopic techniques. We have tested the in vitro antitumor activity of the new complexes against human chronic myelogenous leukemia, K562, a nd human colon adenocarcinoma, COLO 205. In these experiments we can d emonstrate cytotoxicity comparable to that of cisplatin, and surprisin gly, activity of the substitutionally-inert Ru(bpy)(2)(2+) complexes o f Tmca and Col is comparable to that of colchicine itself. It is sugge sted that the antineoplastic activity is predominantly due to the inta ct complexes since solution studies of all the Ru and Pt complexes at room temperature in 0.1 M saline/5% DMSO show no degradation products over 48 h.