Hydroxyurea distracts DNA synthesis by inhibiting ribonucleotide reductase activity. Hydroxyurea itself as well as some of its derivates are used in the treatment of different diseases, such as psoriasis, AIDS and several types of cancers. In this study we synthesized derivatives of hydroxyurea, hydroxybiuret and trihydroxyisocyanuric acid and investigate their effect on two human cell lines and three bacterial strains. The effects of hydroxyurea derivatives on the metabolic activity of monocyte-like (THP-1) and T lymphocyte-like (Jurkat) cell lines were tested using colorimetric CellTiter 96® AQueous One Solution Cell Proliferation Assay. Antimicrobial activity was tested by measuring minimal inhibitory concentrations of the derivatives on three E. coli species: DH5alpha as antibiotic sensitive strain and DH5alpha /pUC18-ermC', BL21(DE3)/pET25b(+)-sgm as strains resistant to macrolide and aminoglycoside antibiotics, respectively. The compounds bearing free OH groups, N-hydroxybiuret, N, N’ , N’ ’ -trihydroxybiuret and 4-(hydroxyaminocarbamoyl)aminobenzoic acid showed the highest effect on the metabolic activity, comparable with N-hydroxyurea effect, while among O-substituted compounds N, N’ -bisbenzyloxyurea and N, N’ , N’ ’ -tribenzyloxybiuret were the most active. The N, N', N''-trihydroxybiuret and 1-(N-hydroxycabamoyl)-benzotriazole were shown to be the only compounds that showed antimicrobial activity in concentrations 10-3 mol dm-3. The in vitro nitric oxide liberation was confirmed with N, N', N''-trihydroxybiuret and 1-(N-hydroxycabamoyl)-benzotriazole decomposition in neutral medium.

Biology,Chemistry,Pharmaceutics