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Development of Novel Bacterial Topoisomerase Inhibitors Assisted by Computational Screening.

ABSTRACT: Multidrug-resistant bacterial infections pose an ever-evolving threat to public health. Since the outset of the antibacterial age, bacteria have developed a multitude of diverse resistance mechanisms that suppress the effectiveness of current therapies. New drug entities, such as Novel Bacterial Topoisomerase Inhibitors (NBTIs), can circumvent this major issue. A computational docking model was employed to predict the binding to DNA gyrase of atypical NBTIs with novel pharmacophores. Synthesis of NBTIs based on computational docking and subsequent antibacterial evaluation against both Gram-positive and Gram-negative bacteria yielded congeners with outstanding anti-staphylococcal activity and varying activity against select Gram-negative pathogens.

SUBMITTER: Powell JW

PROVIDER: S-EPMC11318591 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Development of Novel Bacterial Topoisomerase Inhibitors Assisted by Computational Screening.

Powell Joshua W JW Mann Chelsea A CA Toth Paul D PD Nolan Sheri S Steinert Anja A Ove Clarissa C Seffernick Justin T JT Wozniak Daniel J DJ Kebriaei Razieh R Lindert Steffen S Osheroff Neil N Yalowich Jack C JC Mitton-Fry Mark J MJ

ACS medicinal chemistry letters 20240715 8

Multidrug-resistant bacterial infections pose an ever-evolving threat to public health. Since the outset of the antibacterial age, bacteria have developed a multitude of diverse resistance mechanisms that suppress the effectiveness of current therapies. New drug entities, such as Novel Bacterial Topoisomerase Inhibitors (NBTIs), can circumvent this major issue. A computational docking model was employed to predict the binding to DNA gyrase of atypical NBTIs with novel pharmacophores. Synthesis o ...[more]

PMID: 39140037

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