Some benzoxazoles and benzimidazoles as DNA topoisomerase I and II inhibitors.

Some novel fused heterocyclic compounds of 2, 5-disubstituted-benzoxazole and benzimidazole derivatives, which were previously synthesized by our group, were investigated for their inhibitory activity on both eukaryotic DNA topoisomerase I and II in a cell free system. 2-Phenoxymethylbenzimidazole (17), 5-amino-2-(p-fluorophenyl)benzoxazole (3), 5-amino-2-(p-bromophenyl)benzoxazole (5), 5-nitro-2-phenoxymethyl-benzimidazole (18), 2-(p-chlorobenzyl)benzoxazole (10) and 5-amino-2-phenylbenzoxazole (2) were found to be more potent as eukaryotic DNA topoisomerase I poisons than the reference drug camptothecin having IC(50) values of 14.1, 132.

Some new bi- and ter-benzimidazole derivatives as topoisomerase I inhibitors.

The discovery of DNA topoisomerases has added a new dimension to the study of anticancer drugs. In the last years detailed investigation of bi- and ter-benzimidazole derivatives revealed that these compounds are a new class of topoisomerase I inhibitors that poisons mammalian topoisomerase I. In this context a survey about topoisomerase I poisoning activity and cytotoxicity of bi- and ter-benzimidazoles is given.