Oxiranylmethyloxy or thiiranylmethyloxy-azaxanthones and -acridone analogues as potential topoisomerase I inhibitors

A total of seven new oxyranylmethyloxy or thiiranylmethyloxy group substituted 5-azaxanthones and -acridones analogues were synthesized and tested for their biological activities for cancer cell lines and topoisomerases. Among the compounds, compound 5, 3-thiiranylmethyloxy-1-hydroxy-5-azaxanthone, showed effective topoisomerase I inhibitory activity, 50% and 27% inhibition ratio at 100 and 20 mu M, respectively. This result is the first finding of the function of 5-azaxanthone compounds for topoisomerase I inhibition and can provide a novel skeleton for the anticancer drug development process. (C) 2009 Elsevier Ltd. All rights reserved.