Rational design, synthesis and testing of novel tricyclic topoisomerase inhibitors for the treatment of bacterial infections part 2. Issue 12 (18th September 2020)

• Record Type: Journal Article
• Authors: Kirk, R.; Ratcliffe, A.; Noonan, G.; Uosis-Martin, M.; Lyth, D.; Bardell-Cox, O.; Massam, J.; Schofield, P.; Lyons, A.; Clare, D.; Maclean, J.; Smith, A.; Savage, V.; Mohmed, S.; Charrier, C.; Salisbury, A-M.; Moyo, E.; Ooi, N.; Chalam-Judge, N.; Cheung, J.; Stokes, N. R.; Best, S.; Craighead, M.; Armer, R.; Huxley, A.
• Is Part Of: RSC medicinal chemistry. Volume 11:Issue 12(2020)
• Page Start: 1379
• Page End: 1385
• Publication Date: 2020-09-18
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1039/d0md00175a
• Languages: English
• ISSNs: 2632-8682

Abstract

Abstract : We disclose the discovery of REDX07965, a novel tricyclic topoisomerase inhibitor (NTTI) which has broad spectrum activity, favourable in vitro pharmacokinetic properties and selectivity versus human topoisomerase II. Abstract : Building on our previously-reported novel tricyclic topoisomerase inhibitors (NTTIs), we disclose the discovery of REDX07965, which has an MIC90 of 0.5 μg mL −1 against Staphylococcus aureus, favourable in vitro pharmacokinetic properties, selectivity versus human topoisomerase II and an acceptable toxicity profile. The results herein validate a rational design approach to address the urgent unmet medical need for novel antibiotics.