Hydantoin Derivatives of L- and D-amino acids: Synthesis and Evaluation of Their Antiviral and Antitumoral Activity

Molecules

Zrinka Rajic¹  Branka Zorc¹  Silvana Raic-Malic¹  Katja Ester¹  Marijeta Kralj¹  Krešimir Pavelic¹  Jan Balzarini¹  Erik De Clercq¹ 

[1] ¹Department of Medicinal Chemistry, Faculty of Pharmacy and Biochemistry, A. Kovačića 1, HR-10000 Zagreb, Croatia

关键词: Hydantoin;    L- and D-amino acids;    antiviral activity;    antitumoral activity.;   

DOI  :  10.3390/11110837

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.