We have prepared a set of heterocyclic benzimidazole derivatives bearing amidino substituents at C-5 of benzimidazole ring, by introducing various heterocyclic nuclei (pyridine, N-methyl-pyrrole or imidazole) at C-2, and evaluated their antitumor and antiviral activities. The most pronounced antiproliferative activity was shown with compounds 6 and 9, having imidazolinylamidino-substituent. Interestingly, all compounds show remarkable selectivity towards breast cancer cell line MCF-7. The most distinct and selective antiviral activity towards Coxackieviruses and Echoviruses was observed with compounds having pyridine ring at C-2. Especially interesting was fairly strong activity of 4 and 8 toward adenoviruses, which could be considered as leads against adenoviral replication.

3,5-Disubstituted hydantoin (1,3-imidazolidinedione) derivatives 5a-h were prepared by base induced cyclization of the corresponding N-(1-benzotriazolecarbonyl)-Land 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 (EC 50 = 16 µg/mL; selectivity index: 25). 3-Cyclohexyl-5-phenyl hydantoin (5g) showed inhibitory activity against cervical carcinoma (HeLa, IC 50 = 5.4 µM) and breast carcinoma (MCF-7, IC 50 = 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) (IC 50 = 20−23 µM), but no effect on WI 38. Molecules 2006, 11 838

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