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Hydantoin Derivatives of L- and D-amino acids: Synthesis and Evaluation of Their Antiviral and Antitumoral Activity
Department of Medicinal Chemistry, Faculty of Pharmacy and Biochemistry, A. Kovačića 1, HR-10000 Zagreb, Croatia
Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, Marulićev trg 20, HR-10000 Zagreb, Croatia
Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, HR-10000 Zagreb, Croatia
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-
3000 Leuven, Belgium
* Authors to whom correspondence should be addressed.
Received: 6 October 2006; in revised form: 25 October 2006 / Accepted: 25 October 2006 / Published: 1 November 2006
Abstract: 3,5-Disubstituted hydantoin (1,3-imidazolidinedione) derivatives 5a-h wereprepared 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 andantiviral activities. Among all the compounds evaluated, 3-benzhydryl-5-isopropylhydantoin (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 inhibitoryactivity 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 thecontrary, the 3-benzhydryl-5-phenyl substituted hydantoin derivative 5h showed moderateinhibitory activity towards HeLa, MCF-7, pancreatic carcinoma (MiaPaCa-2), lungcarcinoma (H 460) and colon carcinoma (SW 620) (IC50 = 20−23 μM), but no effect on WI38.
Keywords: Hydantoin; L- and D-amino acids; antiviral activity; antitumoral activity.
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Rajic, Z.; Zorc, B.; Raic-Malic, S.; Ester, K.; Kralj, M.; Pavelic, K.; Balzarini, J.; De Clercq, E.; Mintas, M. Hydantoin Derivatives of L- and D-amino acids: Synthesis and Evaluation of Their Antiviral and Antitumoral Activity. Molecules 2006, 11, 837-848.
Rajic Z, Zorc B, Raic-Malic S, Ester K, Kralj M, Pavelic K, Balzarini J, De Clercq E, Mintas M. Hydantoin Derivatives of L- and D-amino acids: Synthesis and Evaluation of Their Antiviral and Antitumoral Activity. Molecules. 2006; 11(11):837-848.
Rajic, Zrinka; Zorc, Branka; Raic-Malic, Silvana; Ester, Katja; Kralj, Marijeta; Pavelic, Krešimir; Balzarini, Jan; De Clercq, Erik; Mintas, Mladen. 2006. "Hydantoin Derivatives of L- and D-amino acids: Synthesis and Evaluation of Their Antiviral and Antitumoral Activity." Molecules 11, no. 11: 837-848.