Hydantoin Derivatives of l- and d-amino acids: Synthesis and Evaluation of Their Antiviral and Antitumoral Activity

摘要

3,5-Disubstituted hydantoin (1,3-imidazolidinedione) derivatives >5a-h were prepared by base induced cyclization of the corresponding N-(1-benzotriazolecarbonyl)-l- and d--amino acid amides >4a-h. Compounds >5a-h were evaluated for their cytostatic and antiviral activities. Among all the compounds evaluated, 3-benzhydryl-5-isopropyl hydantoin (>5a) showed a weak but selective inhibitory effect against vaccinia virus (EC50 = 16 μg/mL; selectivity index: 25). 3-Cyclohexyl-5-phenyl hydantoin (>5g) showed inhibitory activity against cervical carcinoma (HeLa, IC50 = 5.4 μM) and breast carcinoma (MCF-7, IC50 = 2 μM), but also cytotoxic effects towards human normal fibroblasts (WI 38). On the contrary, the 3-benzhydryl-5-phenyl substituted hydantoin derivative >5h showed moderate inhibitory activity towards HeLa, MCF-7, pancreatic carcinoma (MiaPaCa-2), lung carcinoma (H 460) and colon carcinoma (SW 620) (IC50 = 20−23 μM), but no effect on WI 38.