Open AccessSpiropyrimidinetriones: a Class of DNA Gyrase Inhibitors with Activity against Mycobacterium tuberculosis and without Cross-Resistance to Fluoroquinolones
Author(s) -
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
Publication year - 2022
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.02192-21
Subject(s) - dna gyrase , dna supercoil , mycobacterium tuberculosis , dna , microbiology and biotechnology , topoisomerase iv , topoisomerase , antibacterial agent , sparfloxacin , biology , tuberculosis , ofloxacin , antibiotics , chemistry , genetics , medicine , escherichia coli , ciprofloxacin , dna replication , gene , pathology
Described here is a series of spiropyrimidinetrione (SPT) compounds with activity againstMycobacterium tuberculosis through inhibition of DNA gyrase. The SPT class operates via a novel mode of inhibition, which involves Mg2+ -independent stabilization of the DNA cleavage complex with DNA gyrase and is thereby not cross-resistant with other DNA gyrase-inhibiting antibacterials, including fluoroquinolones.