Original article Design, synthesis and in vitro antimicrobial evaluation of novel Imidazo[1,2-a] pyridine and imidazo[2,1-b][1,3]benzothiazole motifs Taleb H. Al-Tel a, b, * , Raed A. Al-Qawasmeh c , Rania Zaarour b a College of Pharmacy, University of Sharjah, P.O. Box 27272, Sharjah, United Arab Emirates b Sharjah Institute for Medical Research-Cancer Division, University of Sharjah, 27272 Sharjah, United Arab Emirates c Department of Chemistry, University of Jordan, Amman 11942, Jordan article info Article history: Received 31 August 2010 Received in revised form 4 January 2011 Accepted 21 February 2011 Available online 26 February 2011 Keywords: Oxadiazole Benzimidazole Phenyl imidazole Imidazopyridine Imidazo[2,1-b][1,3]benzothiazole Antibacterial Antifungal abstract New antimicrobial agents, imidazo[1,2-a]pyridine and imidazo[2,1-b][1,3]benzothiazole, have been synthesized. Their antimicrobial activities were conducted against various Gram-positive, Gram-negative bacteria and fungi. Compounds 6c, 7a, 10b, 11a, 12b, 14a, 14b, 15a and 15b, exerted strong inhibition of the investigated bacterial and fungal strains compared to control antibiotics amoxicillin and cefixime and the antifungal agent fluconazole. Results from this study showed that the nature of the substituents on the armed aryl groups determines the extent of the activity of the fused imidazopyridine and/or imidazobenzothiazole derivatives. Preliminary structureeactivity observations revealed that bromo- fluoro substituents enhanced the antimicrobial activity significantly compared to other substituents. Ó 2011 Elsevier Masson SAS. All rights reserved. 1. Introduction Despite significant progress in antimicrobial therapy, infectious diseases caused by bacteria and fungi remain a major health concern due to the development of resistance to existing antimi- crobial drugs. The increasing incidence of bacterial resistance to large number of antibacterial agents such as glycopeptides, sulfonamides, b-lactams, nitroimidazoles, quinolones, tetracyclins, chloramphenicol and macrolides is becoming a major concern [1,2]. In particular, the emergence of multiple drug resistant Gram- positive and Gram-negative bacteria has caused life-threatening infectious diseases in many countries around the world [3]. On the other hand, systemic and dermal fungal infections have significantly increased, specifically in patients undergoing organ transplants [4], anticancer chemotherapy or long term treatment with antimicrobial agents [5e7]. Patients with AIDS are immuno suppressed, and very susceptible to life-threatening systemic fungal infections by Candidiasis, Cryptococcosis and Aspergillosis [5,6]. Reports are available on the development of resistance to currently available antifungal azoles in Candida spp., as well as clinical failures in the treatment of fungal infections [5e8]. Furthermore, most of the present antifungal drugs are not effective against invasive Aspergillosis and the only drug of choice in such patients is the injectable amphotericin B [9]. Therefore, there is an increasing need to design new antibacterial and antifungal agents with better activity profile. The aim of this study is therefore, to synthesize hybrid mole- cules through the combination of different pharmacophores for the purpose of obtaining potent antibacterial and antifungal lead compounds. In continuation of an ongoing program aimed at natural product synthesis and preparation of medicinally active structures [10e12], we describe herein an efficient process for the construction of polyfunctionalized imidazo[1,2-a]pyridine and imidazo[2,1-b][1,3]benzothiazole derivatives and their antimicro- bial evaluation. Recent studies from many laboratories implicate the activity of these scaffolds against many of the most common human diseases, including diabetes [13], cancers [14], infection by microorganisms [15], viral infections and an array of neurological syndromes [16]. A literature search indicated that benzimidazoles [17e19], oxadiazoles [20e22] and phenyl imidazoles [23,24] with different substitution patterns possess a wide range of biological activities [25e32]. * Corresponding author. College of Pharmacy, University of Sharjah, 27272 Sharjah, United Arab Emirates. Tel.: þ971 501732950; fax: þ971 6 5585812. E-mail address: taltal@sharjah.ac.ae (T.H. Al-Tel). Contents lists available at ScienceDirect European Journal of Medicinal Chemistry journal homepage: http://www.elsevier.com/locate/ejmech 0223-5234/$ e see front matter Ó 2011 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.ejmech.2011.02.051 European Journal of Medicinal Chemistry 46 (2011) 1874e1881