N-(1,3,4-oxadiazol-2-yl)benzamide analogs, bacteriostatic agents against methicillin- and vancomycin-resistant bacteria.
Clement Opoku-Temeng, George A Naclerio, Haroon Mohammad, Neetu Dayal, Nader S Abutaleb, Mohamed N Seleem, Herman O Sintim
Author Information
Clement Opoku-Temeng: Chemistry Department, Institute for Drug Discovery, Purdue University, West Lafayette, IN, 47907, USA; Graduate Program in Biochemistry, University of Maryland, College Park, MD, 20742, USA.
George A Naclerio: Chemistry Department, Institute for Drug Discovery, Purdue University, West Lafayette, IN, 47907, USA.
Haroon Mohammad: Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, West Lafayette, N47907, USA.
Neetu Dayal: Chemistry Department, Institute for Drug Discovery, Purdue University, West Lafayette, IN, 47907, USA.
Nader S Abutaleb: Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, West Lafayette, N47907, USA.
Mohamed N Seleem: Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, West Lafayette, N47907, USA.
Herman O Sintim: Chemistry Department, Institute for Drug Discovery, Purdue University, West Lafayette, IN, 47907, USA. Electronic address: hsintim@purdue.edu.
Various reports of multidrug-resistant bacteria that are immune to all available FDA-approved drugs demand the development of novel chemical scaffolds as antibiotics. From screening a chemical library, we identified compounds with antibacterial activity. The most potent compounds, F6-5 and F6, inhibited growth of various drug-resistant Gram-positive bacterial pathogens at concentrations ranging from 1 μg/mL to 2 μg/mL. Both compounds were active against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate and vancomycin-resistant S. aureus (VISA and VRSA respectively) and vancomycin-resistant Enterococcus faecalis (VRE). Resistance generation experiments revealed that MRSA could develop resistance to the antibiotic ciprofloxacin but not to F6. Excitingly, F6 was found to be non-toxic against mammalian cells. In a mouse skin wound infection model, F6 was equipotent to the antibiotic fusidic acid in reducing MRSA burden.
