Spiropyrimidinetriones: a Class of DNA Gyrase Inhibitors with Activity against Mycobacterium tuberculosis and without Cross-Resistance to Fluoroquinolones
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
Abstract
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.
Topics & Concepts
DNA gyraseMycobacterium tuberculosisDNAAntibacterial agentMicrobiologyAntibioticsChemistryBiologyTuberculosisBiochemistryEscherichia coliMedicineGenePathologyCancer therapeutics and mechanismsTuberculosis Research and EpidemiologyBioactive Compounds and Antitumor Agents