Ring fusion strategy for the synthesis of anthra[2,3-d]oxazole-2-thione-5,10-dione homologues as DNA topoisomerase inhibitors and as antitumor agents.

The efficient synthesis of mono-substituted anthraquinones and ring fusion into anthra[2,3-d]oxazole-2-thione-5,10-dione derivatives were developed, and all the compounds were tested for their cytotoxicity against PC-3 cancer cell lines. Compounds 8, 14, 17 and 23 were selected by the NCI and 12, 17 and 19 were evaluated for topoisomerase I-mediated DNA relaxation. Among them, 17 appeared to be the most active compound of this series and not only showed higher inhibition when indicated from the low IC50 values against PC-3 cancer cell line but also attenuated the in vitro topoisomerase I-mediated DNA relaxation at low micromolar concentrations. All test compounds exhibited different cytostatic and cytotoxic activities for further developing potential anticancer drugs.