Spiropyrimidinetriones: a Class of DNA Gyrase Inhibitors with Activity against Mycobacterium tuberculosis and without Cross-Resistance to Fluoroquinolones

作者：Gregory S. Basarab, Sandeep R. Ghorpade, Liezl Gibhard, Rudolf Mueller, Mathew Njoroge, Nashied Peton, Preshendren Govender, Lisa M. Massoudi, Gregory T. Robertson, Anne J. Lenaerts, Helena I. Boshoff, Douglas Joerss, Tanya Parish, Thomas F. Durand-Réville, Manos Perros, Vinayak Singh, Kelly Chibale · 发表于：Antimicrobial Agents and Chemotherapy · 年份：2022 · DOI：10.1128/aac.02192-21 · 被引用次数：26 · 研究领域：Cancer therapeutics and mechanisms、Tuberculosis Research and Epidemiology、Bioactive Compounds and Antitumor Agents

Described here is a series of spiropyrimidinetrione (SPT) compounds with activity against Mycobacterium tuberculosis through inhibition of DNA gyrase. The SPT class operates via a novel mode of inhibition, which involves Mg 2+ -independent stabilization of the DNA cleavage complex with DNA gyrase and is thereby not cross-resistant with other DNA gyrase-inhibiting antibacterials, including fluoroquinolones.