title: Synthesis and Evaluation of Selected Benzimidazole Derivatives as Potential Antimicrobial Agents.
abstract: A library of 53 benzimidazole derivatives, with substituents at positions 1, 2 and 5, were synthesized and screened against a series of reference strains of bacteria and fungi of medical relevance. The SAR analyses of the most promising results showed that the antimicrobial activity of the compounds depended on the substituents attached to the bicyclic heterocycle. In particular, some compounds displayed antibacterial activity against two methicillin-resistant Staphylococcus aureus (MRSA) strains with minimum inhibitory concentrations (MICs) comparable to the widely-used drug ciprofloxacin. The compounds have some common features; three possess 5-halo substituents; two are derivatives of (S)-2-ethanaminebenzimidazole; and the others are derivatives of one 2-(chloromethyl)-1H-benzo[d]imidazole and (1H-benzo[d]imidazol-2-yl)methanethiol. The results from the antifungal screening were also very interesting: 23 compounds exhibited potent fungicidal activity against the selected fungal strains. They displayed equivalent or greater potency in their MIC values than amphotericin B. The 5-halobenzimidazole derivatives could be considered promising broad-spectrum antimicrobial candidates that deserve further study for potential therapeutic applications.
authors: Chemistry Department, College of Science, King Saud University, Riyadh 11362, Saudi Arabia. fasmari@ksu.edu.sa.|Centre for Pharmaceutical Engineering Science, Faculty of Life Sciences, University of Bradford, Richmond Road, Bradford BD7 1DP, UK. fasmari@ksu.edu.sa.
authors: Fatmah A S
authors: FA
authors: Alasmary
authors: Centre for Pharmaceutical Engineering Science, Faculty of Life Sciences, University of Bradford, Richmond Road, Bradford BD7 1DP, UK. a.m.snelling@bradford.ac.uk.
authors: Anna M
authors: AM
authors: Snelling
authors: Botany and Microbiology Department, College of Science, King Saud University, Riyadh 11362, Saudi Arabia. mohamedzain@hotmail.com.
authors: Mohammed E
authors: ME
authors: Zain
authors: Department of Pharmaceutical Chemistry, College of Pharmacy, Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia. alafeefy@hotmail.com.
authors: Ahmed M
authors: AM
authors: Alafeefy
authors: Pharmacognosy Department, College of Pharmacy, Salman bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia. amaniawaad@hotmail.com.
authors: Amani S
authors: AS
authors: Awaad
authors: Centre for Pharmaceutical Engineering Science, Faculty of Life Sciences, University of Bradford, Richmond Road, Bradford BD7 1DP, UK. nazira.karodia@wlv.ac.uk.|Faculty of Science and Engineering, University of Wolverhampton, Wulfruna Street, Wolverhampton WV1 1LY, UK. nazira.karodia@wlv.ac.uk.
authors: Nazira
authors: N
authors: Karodia
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D002939:Ciprofloxacin / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D001562:Benzimidazoles; D002939:Ciprofloxacin
keywords: Gram-negative; Gram-positive; antibacterial activity; antifungal activity; benzimidazole; heterocycle; resistance