Discovery and structure–activity relationships of a novel isothiazolone class of bacterial type II topoisomerase inhibitors. Issue 17 (1st September 2016)

• Record Type: Journal Article
• Authors: Cooper, Ian R.; McCarroll, Andrew J.; McGarry, David; Kirkham, James; Pichowicz, Mark; Walker, Rolf; Warrilow, Catherine; Salisbury, Anne-Marie; Savage, Victoria J.; Moyo, Emmanuel; Forward, Henry; Cheung, Jonathan; Metzger, Richard; Gault, Zoe; Nelson, Gary; Hughes, Diarmaid; Cao, Sha; Maclean, John; Charrier, Cédric; Craighead, Mark; Best, Stuart; Stokes, Neil R.; Ratcliffe, Andrew J.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 17(2016)
• Page Start: 4179
• Page End: 4183
• Publication Date: 2016-09-01
• Subjects: ESKAPE pathogens -- Anti-infectives -- Topoisomerases -- DNA gyrase -- Isothiazolone; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.07.061
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: There is an urgent and unmet medical need for new antibacterial drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. During the course of our wider efforts to discover and exploit novel mechanism of action antibacterials, we have identified a novel series of isothiazolone based inhibitors of bacterial type II topoisomerase. Compounds from the class displayed excellent activity against both Gram-positive and Gram-negative bacteria with encouraging activity against a panel of MDR clinical Escherichia coli isolates when compared to ciprofloxacin. Representative compounds also displayed a promising in vitro safety profile.