Naslov
The novel L- and D-amino acid derivatives of hydroxyurea and hydantoins: Synthesis, X-ray crystal structure study, cytostatic and antiviral activity evaluations

Autori
Opačić, Ninoslav ; Barbarić, Monika ; Zorc, Branka ; Cetina, Mario ; Nagl, Ante ; Frković, Danijel ; Kralj, Marijeta ; Pavelić, Krešimir ; Balzarini, Jan ; Andrei, Graciela ; Snoeck, Robert ; De Clerq, Erik ; Raić-Malić, Silvana ; Mintas, Mladen

Izvornik
Journal of medicinal chemistry (0022-2623) 48 (2005), 2; 475-482

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
hydroxyurea ; hydantoins ; amino acid derivatives ; X-ray ; cytostatic and antiviral activity

Sažetak
The novel L- and D-amino acid derivatives of hydroxyurea 5a-o were prepared by aminolysis N-(1-benzotriazolecarbonyl)-amino acid amides 4a-o with hydroxylamine. The hydantoin derivatives 6a-e, m, p were synthesized by base catalysed cyclization of amides 4, common precursor for 5 and 6. X-ray crystal structure analysis shows that the C5 atom in 6e posseses S configuration which is consistent with the configuration of the starting reagent, L-leucine. Among L-amino acid derivatives of hydroxyurea, 5h and 5i inhibited specifically murine leukemia and human T-lymphocytes (IC50: 10-19 μ M) and showed selectivity with respect to normal human fibroblasts (WI 38). D-amino acid derivatives of hydroxyurea 5m and 5o inhibited the growth of all tumor cell lines (IC50: 4.8-83.9 μ M), but not the growth of normal fibroblasts (WI 38 ; IC50: >100 μ M). Results on antiviral evaluations showed that N-(1-benzotriazolecarbonyl)-amino acid amide 4m and hydantoin 6m had marked activity against the Davis strain of CMV (4m, EC50: 3.2 μ g/mL and 6m, EC50: 4.0 μ g/mL). However, these compounds showed also rather expressed cytotoxicity (4m, CC50: 43.4 μ g/mL and 6m, CC50: 12.5 μ g/mL).

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti, Farmacija

POVEZANOST RADA