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1,3-Dioxane-Linked Novel Bacterial Topoisomerase Inhibitors: Expanding Structural Diversity and the Antibacterial Spectrum.

ABSTRACT: Antibacterial resistance continues its devastation of available therapies. Novel bacterial topoisomerase inhibitors (NBTIs) offer one solution to this critical issue. Two series of amine NBTIs bearing tricyclic DNA-binding moieties as well as amide NBTIs with a bicyclic DNA-binding moiety were synthesized and evaluated against methicillin-resistant Staphylococcus aureus (MRSA). Additionally, these compounds and a series of bicyclic amine analogues displayed high activity against susceptible and drug-resistant Neisseria gonorrhoeae, expanding the spectrum of these dioxane-linked NBTIs.

SUBMITTER: Lu Y

PROVIDER: S-EPMC9189870 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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1,3-Dioxane-Linked Novel Bacterial Topoisomerase Inhibitors: Expanding Structural Diversity and the Antibacterial Spectrum.

Lu Yanran Y Mann Chelsea A CA Nolan Sheri S Collins Jessica A JA Parker Elizabeth E Papa Jonathan J Vibhute Sandip S Jahanbakhsh Seyedehameneh S Thwaites Mary M Hufnagel David D Hazbón Manzour H MH Moreno Jane J Stedman Timothy T TT Wittum Thomas T Wozniak Daniel J DJ Osheroff Neil N Yalowich Jack C JC Mitton-Fry Mark J MJ

ACS medicinal chemistry letters 20220509 6

Antibacterial resistance continues its devastation of available therapies. Novel bacterial topoisomerase inhibitors (NBTIs) offer one solution to this critical issue. Two series of amine NBTIs bearing tricyclic DNA-binding moieties as well as amide NBTIs with a bicyclic DNA-binding moiety were synthesized and evaluated against methicillin-resistant Staphylococcus aureus (MRSA). Additionally, these compounds and a series of bicyclic amine analogues displayed high activity against susceptib ...[more]

PMID: 35707162

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Oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad spectrum antibacterial agents.

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