Acta Pharm. 63 (2013) 175-191
Original research paper
Synthesis, antibacterial and cytotoxic activity
evaluation of hydroxyurea derivatives
IVAN
KOS, MILENA JADRIJEVIĆ-MLADAR TAKAČ, IVAN BUTULA, MLADEN BIRUŠ, GORDANA
MARAVIĆ-VLAHOVIČEK and SANJA DABELIĆ
University of Zagreb, Faculty of Pharmacy and
Biochemistry, Zagreb, Croatia
Accepted February 28, 2013
Synthesis and biological evaluation for a series (N = 16) of cyclic and acyclic hydroxyurea derivatives including benzotriazole-, isocyanuirc acid- and biuret-containing compounds, are disclosed. 1-N-(benzyloxycarbamoyl)benzotriazole was used as 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., strain susceptible to antibiotics, strain resistant to macrolide antibiotics and strain resistant to aminoglycoside antibiotics. Six compounds (three acyclic and three cyclic hydroxyureas) showed the growth inhibition of 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 on human acute T cell leukemia Jurkat cell line. 1-(N-hydroxycarbamoyl)benzotriazole (5) increased 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.
Keywords: hydroxyurea derivatives, synthesis, antibacterial activity,
cytotoxicity