title: Synthesis, antibacterial and cytotoxic activity evaluation of hydroxyurea derivatives.
abstract: 5 Synthesis and biological evaluation of a series (N = 16) of cyclic and acyclic hydroxyurea derivatives, including benzotriazole-, isocyanuric acid- and biuret-containing compounds, are disclosed. 1-N-(benzyloxycarbamoyl)benzotriazole was used as a benzyloxyisocyanate donor, a useful intermediate in the preparation of substituted hydroxyurea. Antibacterial activities of synthesized hydroxyurea derivatives were tested on three E. coli strains, i.e., a strain susceptible to antibiotics, a strain resistant to macrolide antibiotics and a strain resistant to aminoglycoside antibiotics. Six compounds (three acyclic and three cyclic hydroxyureas) showed growth inhibition of the tested E. coli strains, with different specificity toward each strain. Results of the cytotoxic activity evaluation revealed that twelve out of sixteen test compounds were cytotoxic to human acute monocytic leukemia THP-1 and/or human acute T cell leukemia Jurkat cell line. 1-(N-hydroxycarbamoyl) benzotriazole () increased the metabolic activity of both cell lines. Two compounds, 1-(N-hydroxycarbamoyl) benzotriazole (5) and N,N',N''-trihydroxybiuret (15), were identified as potential NO donors.
authors.affiliation: Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Kos
authors.forename: Milena
authors.initials: M
authors.lastname: Jadrijević-Mladar
authors.forename: Ivan
authors.initials: I
authors.lastname: Butula
authors.forename: Mladen
authors.initials: M
authors.lastname: Biruš
authors.forename: Gordana
authors.initials: G
authors.lastname: Maravić-Vlahoviček
authors.forename: Sanja
authors.initials: S
authors.lastname: Dabelić
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001737:Biuret / Q000138:chemical synthesis / Q000494:pharmacology; D004926:Escherichia coli / Q000145:classification / Q000187:drug effects*; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives*; D007536:Isomerism; D019169:Jurkat Cells / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D014227:Triazines; D014230:Triazoles; C012771:benzotriazole; D001737:Biuret; C004632:cyanuric acid; D006918:Hydroxyurea