Background: Some 2-thioxoimidazolidinones have been reported as anti-prostate and anti-breast cancer
agents through their inhibitory activity on topoisomerase I that is considered as a potential chemotherapeutic target.
Objective: A new series of 3,5-disubstituted-2-thioxoimidazolidinone derivatives 10a-f and their S-methyl analogs
11a-f were designed, synthesized and evaluated for cytotoxicity against human prostate cancer cell line (PC-3),
human breast cancer cell line (MCF-7) and non-cancerous human lung fibroblast cell line (WI-38).
Results and Method: While compounds 10a-f showed a broad range of activities against PC-3 and MCF-7 cell lines
(IC50 = 34.0 – 186.9 and 24.6 – 147.5 µM respectively), the S-methyl analogs 11a-f showed (IC50 = 22.7 – 198.5 and
16.9 – 188.2 µM respectively) in comparison with 5-fluorouracil (IC50 = 60.7 and 40.7 µM respectively). 11c (IC50 =
22.7 and 29.2 µM) and 11f (IC50 = 28.7 and 16.9 µM) were the most potent among all compounds against both PC-3
and MCF-7 respectively with no cytotoxicity against WI-38.
Conclusion: The newly synthesized compounds showed good activity against PC-3 and MCF-7 cell lines in
comparison with 5-fluorouracil. Compounds 11c and 11f bound with human topoisomerase I similar to its known
inhibitors and significantly inhibited its DNA relaxation activity in a dose dependent manner which may rationalize
their molecular mechanism as cytotoxic agents.