title: Novel lipophilic hydroxyurea derivatives: synthesis, cytostatic and antiviral activity evaluations.
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.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Biochemistry, A. Kovacića 1, HR-10 000 Zagreb, Croatia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Perković
authors.forename: Ivan
authors.initials: I
authors.lastname: Butula
authors.forename: Branka
authors.initials: B
authors.lastname: Zorc
authors.forename: Karlo
authors.initials: K
authors.lastname: Hock
authors.forename: Sandra
authors.initials: S
authors.lastname: Kraljević Pavelić
authors.forename: Kresimir
authors.initials: K
authors.lastname: Pavelić
authors.forename: Erik De
authors.initials: ED
authors.lastname: Clercq
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Mladen
authors.initials: M
authors.lastname: Mintas
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D000998:Antiviral Agents / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D014780:Viruses / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D006918:Hydroxyurea