Indolin-2-one Nitroimidazole Antibiotics Exhibit an Unexpected Dual Mode of Action
Till Reinhardt, Kyu M. Lee, Lukas Niederegger, Corinna R. Hess, Stephan A. Sieber
Abstract
reduction. Overall, this study unravels that indolin-2-one-functionalized nitroimidazoles feature an unexpected dual MoA: first, the direct inhibition of the topoisomerase IV and second the classic nitroimidazole MoA of reductive bioactivation leading to damaging reactive species. Importantly, this dual MoA impairs resistance development. Given the clinical application of this compound class, the new mechanism could be a starting point to mitigate resistance.
Topics & Concepts
NitroimidazoleTopoisomeraseChemistryTopoisomerase IVDNA damageMode of actionBacteriaDNABiochemistryDNA gyraseMicrobiologyBiologyEscherichia coliGeneticsOrganic chemistryGeneAntibiotic Resistance in BacteriaCancer therapeutics and mechanismsBacteriophages and microbial interactions