SYNTHESIS AND EVALUATION OF TERBENZIMIDAZOLES AS TOPOISOMERASE-I INHIBITORS

The synthesis and pharmacological activity of a series of terbenzimida zoles are described. The ability of these derivatives to induce DNA cl eavage in the presence of topoisomerase I was evaluated in vitro. Thes e analogs were also assayed for their cytotoxicity in RPMI 8402 cells and the camptothecin-resistant CPT-K5 cells. In addition the potential for these compounds to serve as substrates for MDR1 was also determin ed. Several terbenzimidazoles exhibited similar cytotoxicity against v ariants of human tumor cells that either overexpress MDR1 or are campt othecin-resistant.