{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:17:55Z","timestamp":1791148675180,"version":"4.1.0"},"reference-count":17,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2006,11,1]],"date-time":"2006-11-01T00:00:00Z","timestamp":1162339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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 \u03bcg\/mL; selectivity index: 25). 3-Cyclohexyl-5-phenyl hydantoin (5g) showed inhibitoryactivity against cervical carcinoma (HeLa, IC50 = 5.4 \u03bcM) and breast carcinoma (MCF-7,IC50 = 2 \u03bcM), 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\u221223 \u03bcM), but no effect on WI38.<\/jats:p>","DOI":"10.3390\/11110837","type":"journal-article","created":{"date-parts":[[2008,10,25]],"date-time":"2008-10-25T13:32:11Z","timestamp":1224941531000},"page":"837-848","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Hydantoin Derivatives of L- and D-amino acids: Synthesis and Evaluation of Their Antiviral and Antitumoral Activity"],"prefix":"10.3390","volume":"11","author":[{"given":"Zrinka","family":"Rajic","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy and Biochemistry, A. Kova\u010di\u0107a 1, HR-10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branka","family":"Zorc","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy and Biochemistry, A. Kova\u010di\u0107a 1, HR-10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana","family":"Raic-Malic","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, Maruli\u0107ev trg 20, HR-10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Ester","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Ru\u0111er Bo\u0161kovi\u0107 Institute, Bijeni\u010dka cesta 54, HR-10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijeta","family":"Kralj","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Ru\u0111er Bo\u0161kovi\u0107 Institute, Bijeni\u010dka cesta 54, HR-10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kre\u0161imir","family":"Pavelic","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Ru\u0111er Bo\u0161kovi\u0107 Institute, Bijeni\u010dka cesta 54, HR-10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Balzarini","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B- 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"De Clercq","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B- 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mladen","family":"Mintas","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, Maruli\u0107ev trg 20, HR-10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2006,11,1]]},"reference":[{"key":"ref_1","unstructured":"Williams, D.A., and Lemke, T.L. (2002). Foye's Principles of Medicinal Chemistry, Lippincott Williams & Wilkins. [5th ed.]."},{"key":"ref_2","unstructured":"Kleemann, A., Engel, J., Kutscher, B., and Reichert, D. (2001). Pharmaceutical Substances, Synthesis, Patents, Applications, Thieme. [4th ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"69","DOI":"10.2174\/1568026053386944","article-title":"New anticonvulsant agents","volume":"5","author":"Malawska","year":"2005","journal-title":"Curr. Topics Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S0928-0987(00)00200-1","article-title":"Mitomycin antitumor compounds. Part 1. CD studies on their molecular structure","volume":"12","author":"Fiallo","year":"2001","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1002\/pro.5560070409","article-title":"The structure of a glycogen phosphorylase glucopyranose spirohydantoin complex at 1.8 angstrom resolution and 100 k \u2013 the role of the water structure and its contribution to binding","volume":"7","author":"Gregoriou","year":"1998","journal-title":"Protein Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1016\/S0008-6215(02)00217-3","article-title":"Syntheses of hydantocidin and C-2 thioxohydantocidin","volume":"337","author":"Shiozaki","year":"2002","journal-title":"Carbohyd. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1021\/jm040869i","article-title":"The novel l- and d-amino acid derivatives of hydroxyurea and hydantoins: synthesis, X-ray crystal structure study, and cytostatic and antiviral activity evaluations","volume":"48","author":"Zorc","year":"2005","journal-title":"J. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1399-3011.2005.00276.x","article-title":"Synthesis and X-ray crystal structure study of the hydroxyurea and hydantoin derivatives of l-valine","volume":"66","author":"Zorc","year":"2005","journal-title":"J. Peptide Res."},{"key":"ref_9","first-page":"441","article-title":"Reaktionen mit N-(1-Benzotriazolylcarbonyl)-aminosauren. I. Synthese von Hydantoinen und Hydantoinsauren-amiden","volume":"54","author":"Zorc","year":"1981","journal-title":"Croat. Chem. Acta"},{"key":"ref_10","first-page":"3506","article-title":"A new method of preparation of 3,5-disubstituted hydantoins","volume":"34","author":"Maslova","year":"1964","journal-title":"Zh. Obshch. Khim."},{"key":"ref_11","first-page":"215","article-title":"Side reactions during the removal of protecting groups of N-(protected aminoacyl)urea derivatives","volume":"98","author":"Friss","year":"1978","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_12","first-page":"435","article-title":"Reaktionen mit 1-Benzotriazol carbonsaurechlorid. VII. Die Umsetzung mit Aminosauren","volume":"54","author":"Butula","year":"1981","journal-title":"Croat. Chem. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/323464a0","article-title":"A novel selective broad-spectrum anti-DNA virus agent","volume":"323","author":"Rosenberg","year":"1986","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1097\/00002030-199101000-00003","article-title":"9-(2-Phosphonylmethoxyethyl)adenine (PMEA) efficiently inhibits retrovirus replication in vitro and simian immunodeficiency virus infection in Rhesus monkeys","volume":"5","author":"Balzarini","year":"1991","journal-title":"AIDS"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0026-895X(25)13487-1","article-title":"Thymidylate synthetase as target enzyme for the inhibitory activity of 5-substituted 2'-deoxyuridines on mouse leukemia L1210 cell growth","volume":"19","author":"Balzarini","year":"1981","journal-title":"Mol. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1002\/ddr.430340203","article-title":"Some practical considerations and applications of the National Cancer Institute In vitro anticancer drug discovery screen","volume":"34","author":"Boyd","year":"1995","journal-title":"Drug Dev. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays","volume":"65","author":"Mossman","year":"1983","journal-title":"Immun. Methods"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/11\/11\/837\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T22:24:45Z","timestamp":1760221485000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/11\/11\/837"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,11,1]]},"references-count":17,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2006,11]]}},"alternative-id":["11110837"],"URL":"https:\/\/doi.org\/10.3390\/11110837","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,11,1]]}}}