Rational design, synthesis and testing of novel tricyclic topoisomerase inhibitors for the treatment of bacterial infections part 2.
R KirkA RatcliffeG NoonanM Uosis-MartinD LythO Bardell-CoxJ MassamP SchofieldA LyonsD ClareJ MacleanA SmithVictoria J SavageS MohmedC CharrierA-M SalisburyE MoyoN OoiN Chalam-JudgeJ CheungN R StokesS BestM CraigheadR ArmerA HuxleyPublished in: RSC medicinal chemistry (2020)
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.