Benzimidazole analogs as WTA biosynthesis inhibitors targeting methicillin resistant Staphylococcus aureus. Issue 19 (1st October 2016)

• Record Type: Journal Article
• Authors: Yang, Shu-Wei; Pan, Jianping; Yang, Christine; Labroli, Marc; Pan, Weidong; Caldwell, John; Ha, Sookhee; Koseoglu, Sandra; Xiao, Jing C.; Mayhood, Todd; Sheth, Payal R.; Garlisi, Charles G.; Wu, Jin; Lee, Sang Ho; Wang, Hao; Tan, Christopher M.; Roemer, Terry; Su, Jing
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 19(2016)
• Page Start: 4743
• Page End: 4747
• Publication Date: 2016-10-01
• Subjects: WTA -- Wall teichoic acid -- Antibacterial -- MRSA; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.08.036
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: A series of benzimidazole analogs have been synthesized and displayed potent WTA inhibitory activity and antibacterial activity in combination with imipenem. Substitution on benzimidazole core has been explored to identify a potent WTA inhibitor21 . Abstract: A series of benzimidazole analogs have been synthesized to improve the profile of the previous lead compounds tarocin B and1 . The syntheses, structure–activity relationships, and selected biochemical data of these analogs are described. The optimization efforts allowed the identification of21, a fluoro-substituted benzimidazole, exhibiting potent TarO inhibitory activity and typical profile for a wall teichoic acid (WTA) biosynthesis inhibitor. Compound21 displayed a potent synergistic and bactericidal effect in combination with imipenem against diverse methicillin-resistant Staphylococci.