Synthesis and Antibacterial Activity of Some 2-Substituted Tinidazole Analogues

Abstract

2-Substituted tinidazole analogues were designed, synthesized and characterized. The synthesized compounds were tested for their antibacterial activity against Gram-positive (B. subtilis and S. aureus) and Gram-negative (E. coli (entero pathogen) and S. typhimurium) bacteria using agar well diffusion method. In the present study the synthesis of new 2-substituted tinidazole analogues containing (a) an α-keto group IVa-IVc (b) oxime group in side chains which enhances antibacterial profile, Va and Vb, and (c) an electron withdrawing cyano function in place of a CH3 group at position 2, VIII, is reported. The 2-substituted tinidazole analogues IVa-IVc were synthesized by nuclephilic substitution reaction of tinidazole and acid chloride in the presence of triethylamine base. Va and Vb, which are oximes of IVa and IVb, respectively, were synthesized by refluxing IVa or IVb with hydroxylamine hydrochloride in ethanol. Compound VIII was synthesized by reacting IVa with potassium nitrite in cold aqueous glacial acetic acid solution. Among the compounds synthesized, compound VIII displayed a good antibacterial activity against all the bacterial strains tested. All the synthesized compounds were found to have weaker antibacterial activity when compared to the activities of the standard drugs metronidazole and tinidazole.

Keywords: tinidazole, antibacterial activity, 5-nitroimidazole, α-ketoderivatives, oximes

Ethiopian Pharmaceutical Journal Vol. 25 (1) 2007: pp. 43-50