New Imidazole-4-one and Imidazolidine-2,4-dione analogs: design, synthesis, antitumor activity, and molecular modeling study


Selwan M. El-Sayed, Mahmoud B. El-Ashmawy, Said M. Bayoumi, Ghada S. Hassan, Hussein I. El-Subbagh

Objectives: New hybrids of 4H-imidazole-4-one and imidazolidine-2,4-dione were designed, synthesized, and evaluated for their antitumor activity in an attempt to reach an active antitumor agent with potentiated activity and selectivity toward cancerous cells. Methods: Compounds 10–26 and 42–61 were synthesized and tested for their in vitro antitumor activity against prostate PC-3, colorectal HCT-116, breast MCF-7, and Hela cancer cell lines, using standard tetrazolium bromide assay. Key findings: Compounds 12, 46, and 54 showed remarkable broad-spectrum cytotoxic potency with median IC50 values of 7.7, 7.2, and 8.9 μM, respectively. Structure–activity correlation revealed that the 4-methyl group at 3-(4-methyl-phenyl)-thiazolyl function, 4-methoxy moiety on the 5-benzylidene group at the 4H-imidazole-4-one and unsubstituted benzoyl function at position-3 of the imidazolidine-2,4-dione favor the cytotoxic activity. Conclusions: Molecular modeling study results were in consistency with the obtained cytotoxicity results. The investigated compounds could be used as template models for further optimization.