4区 · 医学
Article
作者: Charrier, Cédric ; Craighead, Mark ; Best, Stuart ; Matthews, Teresa ; Dick, Emma ; Walker, Rolf ; Savage, Victoria J ; Stokes, Neil R ; Newman, Rebecca ; Smith, Andrew ; Ooi, Nicola ; Smith, Oliver ; Kirkham, James ; Salisbury, Anne-Marie ; Ratcliffe, Andrew J ; Bunt, Adam ; Dauncey, Elizabeth ; Orr, David ; Morrison, Ian ; Blades, Kevin ; Lyons, Amanda ; Cooper, Ian R ; Butler, Hayley S ; Finlayson, Jonathan ; Moyo, Emmanuel
There is an increasingly urgent and unmet medical need for novel antibiotic drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. Novel bacterial type II topoisomerase inhibitors (NBTIs) are of high interest due to limited cross-resistance with fluoroquinolones, however analogues with Gram-negative activity often suffer from hERG channel inhibition. A novel series of bicyclic-oxazolidinone inhibitors of bacterial type II topoisomerase were identified which display potent broad-spectrum anti-bacterial activity, including against MDR strains, along with an encouraging in vitro safety profile. In vivo proof of concept was achieved in a A. baumannii mouse thigh infection model.