ACS Infectious Diseases p. 1115 - 1128 (2019)
Update date:2022-08-17
Topics:
Li, Linsen
Okumu, Antony A.
Nolan, Sheri
English, Anthony
Vibhute, Sandip
Lu, Yanran
Hervert-Thomas, Katherine
Seffernick, Justin T.
Azap, Lovette
Cole, Serena L.
Shinabarger
Koeth, Laura M.
Lindert, Steffen
Yalowich, Jack C.
Wozniak, Daniel J.
Mitton-Fry, Mark J.
The development of new therapies to treat methicillin-resistant Staphylococcus aureus (MRSA) is needed to counteract the significant threat that MRSA presents to human health. Novel inhibitors of DNA gyrase and topoisomerase IV (TopoIV) constitute one highly promising approach, but continued optimization is required to realize the full potential of this class of antibiotics. Herein, we report further studies on a series of dioxane-linked derivatives, demonstrating improved antistaphylococcal activity and reduced hERG inhibition. A subseries of analogues also possesses enhanced inhibition of the secondary target, TopoIV.
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