Abdeen, SanofarKunkle, TrentSalim, NilshadRay, Anne-MarieMammadova, NajibaSummers, CoreyStevens, MckaylaAmbrose, Andrew J.Park, YangshinSchultz, Peter G.Horwich, Arthur L.Hoang, QuyenChapman, EliJohnson, Steven M.2018-09-172018-09-172018Abdeen, S., Kunkle, T., Salim, N., Ray, A.-M., Mammadova, N., Summers, C., … Johnson, S. M. (2018). Sulfonamido-2-arylbenzoxazole GroEL/ES inhibitors are potent antibacterials against methicillin-resistant Staphylococcus aureus (MRSA). Journal of Medicinal Chemistry, 61 (16), pp 7345–7357. https://doi.org/10.1021/acs.jmedchem.8b00989https://hdl.handle.net/1805/17332Extending from a study we recently published examining the antitrypanosomal effects of a series of GroEL/ES inhibitors based on a pseudosymmetrical bis-sulfonamido-2-phenylbenzoxazole scaffold, here, we report the antibiotic effects of asymmetric analogs of this scaffold against a panel of bacteria known as the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). While GroEL/ES inhibitors were largely ineffective against K. pneumoniae, A. baumannii, P. aeruginosa, and E. cloacae (Gram-negative bacteria), many analogs were potent inhibitors of E. faecium and S. aureus proliferation (Gram-positive bacteria, EC50 values of the most potent analogs were in the 1–2 μM range). Furthermore, even though some compounds inhibit human HSP60/10 biochemical functions in vitro (IC50 values in the 1–10 μM range), many of these exhibited moderate to low cytotoxicity to human liver and kidney cells (CC50 values > 20 μM).enPublisher PolicyGroELGroESHSP60Article