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