26 Anti-Infective Agents, 2012, 10, 26-33 2211-3626/12 $58.00+.00 © 2012 Bentham Science Publishers Antibacterial Activity of Some New Azole Compounds S. Khabnadideh*, Z. Rezaei; Y. Ghasemi and N. Montazeri-Najafabady Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Abstract: The development of antimicrobial agents to treat infections has been one of the most notable medical achieve- ments of the past century. Despite the growing list of azoles, their clinical value has been limited by their relatively high risk of toxicity and the emergence of drug resistance. This necessitates the development of more effective broad spectrum antimicrobials with fewer side effects. We previously described the design and synthesis of some new azole derivatives in both imidazole and triazole groups. Here we selected 30 analogues of them in 4 different categories (imidazoles (1), ben- zimidazoles (2), triazoles (3) and benztriazoles (4)) and investigated their antibacterial activity against different species of gram positive and gram negative microorganisms. Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Bacillus subtilis as gram positive and Escherichia coli, Salmonella typhi, Shigella sonnei, Pseudomonas aeroginosa and Proteus vulgaris as gram negative bacteria were chosen. Disc plate method and serial dilution assay were used to establish the minimum inhibitory concentration of the above compounds. The results show compounds 1-dodecyl- 2-methyl-1H-imidazole (1g), 2-(1H-1-imidazolyl)-1-cyclohexanol (1a) and 2-(2-methyl-4-nitro-1H-1-imidazolyl)-1- cyclohexanol (1o) had desirable antibacterial activity on both gram positive and gram negative species. Compounds 1- trityl-1H-benzo (d) imidazole (2a) and 1-octyl-1H-1,2,4-triazole (3b) had higher effect for gram positive and gram nega- tive bacteria respectively. Compounds 2-methyl-1- nonyl-1H-imidazole (1f) and 1-butyl-2-methyl-4-nitro-1H-imidazole (1l) had moderate activity for gram negative bacteria. Keywords: Imidazole, triazole, benzimidazole, benztriazole, antibacterial. INTRODUCTION The rapid development and spread of antimicrobial resis- tance has become an increasingly serious public health prob- lem in a wide range of infectious diseases [1]. In spite of a large number of antibiotics and chemotherapeutics available for medical use, the antimicrobial resistance created a sub- stantial medical need for new classes of antimicrobial agents in the last decades. In view of the above, the design and syn- thesis of newer antimicrobials will always remain an area of immense significance [2]. Among the important pharma- cophores responsible for antimicrobial activity, the azole scaffold is still considered a viable lead structure for the syn- thesis of more efficacious and broad spectrum antimicrobial agents. Azoles (imidazole and triazole derivatives) inhibit the synthesis of sterols in fungi by inhibiting cytochrome P 450 -dependent 14-lanosterol demethylase, which removes the methyl group on C 14 of lanosterol, a key intermediate step in the formation of ergosterol in the fungal cell mem- brane [3]. Additionally, it has been reported that remarkable antibacterial activity against methicillin-resistant strains of Staphylococcus aureus was ascribed to some azoles, particu- larly miconazole. Furthermore, some azoles were proved to be effective inhibitors of enoyl acyl carrier protein reductase (FabI), a novel antibacterial target. However, the frequent use of azoles has resulted in clinically resistant strains of fungi and bacteria. Various attempts have been undertaken to *Address correspondence to this author at the Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Tel: +98-711-2424127-8; Fax: +98-711-2424126; E-mail: khabns@sums.ac.ir modify the structures of the so far effective azole drugs in order to improve their antimicrobial potency and selectivity [3]. Nevertheless, there are still major weaknesses in their spectra, potencies, safety, and pharmacokinetic properties [4]. We previously described the design and synthesis of some new alkylimidazole [5], clotrimazole [6,7], metronida- zole [8], and triazole [9] analogous and we also evaluated their antifungal and antigyardiasis activity as well. The aim of this study is to evaluate their antibacterial activity. For this purpose we divided 30 new analogues of them in to 4 differ- ent categories (imidazole (1), benzimidazole (2), triazole (3) and benztriazole (4)). Azole cores are imidazole, 2-methyl imidazole or 2-methyl-4-nitro imidazole of the compounds in the category 1, benzimidazole in category 2, triazole and benztriazole in categories 3 and 4 respectively. All of the compounds contain a substitution at N 1 position of the azole ring. This substitution is an alkyl chain or a triphenyl methyl with or without one or two methoxy groups at para position of the phenyl rings. The chemical structures of all com- pounds are showed in Table 1. Antibacterial evaluations were carried out using different species of gram positive and gram negative microorganisms. The antibacterial activities of the above compounds were compared to ampicillin and gen- tamicin as positive control. MATERIALS AND METHODS All chemicals and solvents were purchased from Merck. New synthesized compounds were prepared in the Depart- ment of Medicinal Chemistry, Faculty of Pharmacy, Shiraz University of Medical Sciences (Table 1). Different species of microorganisms were prepared in the Department of Bio-