Novel Lipophilic Hydroxyurea Derivatives: Synthesis, Cytostatic and Antiviral Activity Evaluations
Identifieur interne : 000481 ( Istex/Curation ); précédent : 000480; suivant : 000482Novel Lipophilic Hydroxyurea Derivatives: Synthesis, Cytostatic and Antiviral Activity Evaluations
Auteurs : Ivana Perkovi [Croatie] ; Ivan Butula [Croatie] ; Branka Zorc [Croatie] ; Karlo Hock [Croatie] ; Sandra Kraljevi Paveli [Croatie] ; Krešimir Paveli [Croatie] ; Erik De Clercq [Belgique] ; Jan Balzarini [Belgique] ; Mladen Mintas [Croatie]Source :
- Chemical Biology & Drug Design [ 1747-0277 ] ; 2008-06.
Abstract
The novel hydroxyurea derivatives of l‐ and d‐amino acid amides 5a–l were prepared by aminolysis of N‐(1‐benzotriazolecarbonyl)‐amino acid amides 4a–f with O‐benzylhydroxylamine and N‐methylhydroxylamine and evaluated for their antiviral and cytostatic activity against malignant tumor cell lines and normal human fibroblasts. Compounds 5a, 5c, 5e and 5k showed the highest antiproliferative effects against all tumor cell lines tested. The strongest non‐specific cytostatic activities against HeLa cells were affected by compounds 5a, 5c, 5e and 5k on MCF‐7 cells by 5c, 5e and 5k and MIA PACa‐2 cells by 5c and 5k. Differential effects at micromolar concentrations were observed for compounds 5a, 5c, 5e, 5k and 5l in Hep G2 cells, for compounds 5c, 5e, 5k and 5l in PC‐3 cells and for compounds 5e, 5k and 5l in SW 620 cells.
Url:
DOI: 10.1111/j.1747-0285.2008.00660.x
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<front><div type="abstract" xml:lang="en">The novel hydroxyurea derivatives of l‐ and d‐amino acid amides 5a–l were prepared by aminolysis of N‐(1‐benzotriazolecarbonyl)‐amino acid amides 4a–f with O‐benzylhydroxylamine and N‐methylhydroxylamine and evaluated for their antiviral and cytostatic activity against malignant tumor cell lines and normal human fibroblasts. Compounds 5a, 5c, 5e and 5k showed the highest antiproliferative effects against all tumor cell lines tested. The strongest non‐specific cytostatic activities against HeLa cells were affected by compounds 5a, 5c, 5e and 5k on MCF‐7 cells by 5c, 5e and 5k and MIA PACa‐2 cells by 5c and 5k. Differential effects at micromolar concentrations were observed for compounds 5a, 5c, 5e, 5k and 5l in Hep G2 cells, for compounds 5c, 5e, 5k and 5l in PC‐3 cells and for compounds 5e, 5k and 5l in SW 620 cells.</div>
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