Structural highlights
Function[GYRB_STAAN] DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings (By similarity). Publication Abstract from PubMedDuring the course of our research to find novel mode of action antibacterials, we discovered a series of hydroxyl tricyclic compounds that showed good potency against Gram-positive and Gram-negative pathogens. These compounds inhibit bacterial type IIA topoisomerases. Herein we will discuss structure-activity relationships in this series and report advanced studies on compound 1 (GSK966587) which demonstrates good PK and in vivo efficacy properties. X-ray crystallographic studies were used to provide insight into the structural basis for the difference in antibacterial potency between enantiomers. Novel hydroxyl tricyclics (e.g., GSK966587) as potent inhibitors of bacterial type IIA topoisomerases.,Miles TJ, Hennessy AJ, Bax B, Brooks G, Brown BS, Brown P, Cailleau N, Chen D, Dabbs S, Davies DT, Esken JM, Giordano I, Hoover JL, Huang J, Jones GE, Kusalakumari Sukmar SK, Spitzfaden C, Markwell RE, Minthorn EA, Rittenhouse S, Gwynn MN, Pearson ND Bioorg Med Chem Lett. 2013 Jul 17. pii: S0960-894X(13)00847-0. doi:, 10.1016/j.bmcl.2013.07.013. PMID:23968823[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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