In 2017, the Centers for Disease Control and Prevention (CDC) estimated that approximately 35,000 people died from infections caused by drug-resistant bacterial pathogens at an annual infection rate of about 2.8 million. Yet, various reports of multidrug-resistant bacteria that are immune to all available FDA-approved drugs demand the development of novel chemical scaffolds as antibiotics. Our laboratory focuses on the discovery of novel compounds to combat the urgent threats of antibiotic-resistant bacteria. We have developed a novel class of sulfonamide containing N-(1,3,4-oxadiazol-2-yl)benzamides which potently inhibit Staphylococcus aureus lipoteichoic acid (LTA) biosynthesis with minimum inhibitory concentrations (MICs) of 0.25 µg/mL. Additonally, we have discovered trifluoromethoxy (OCF3), trifluoromethylthio (SCF3) and pentafluorosulfanyl (SF5) containing (1,3,4-oxadiazol-2-yl)benzamides exhibiting strong antibacterial activities against a wide-range of clinically important bacterial pathogens such as methicillin-resistant S. aureus (MRSA), vancomycin resistant enterococcus (VRE), Clostridioides difficile (C. difficile), and Neisseria gonorrhoeae (N. gonorrhoeae) with MICs as low as 0.003 µg/mL. Furthermore, these N-(1,3,4-oxadiazol-2-yl)benzamides are non-toxic to mammalian cells, inhibit biofilm formation, clear intracellular MRSA in infected macrophages, behave synergistically or additively with antibiotics, and are efficacious in mouse models of MRSA and C. difficile infection.

Novel N-(1,3,4-oxadiazol-2-yl)benzamides as anti-bacterial agents

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.