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Publication

Identification and profiling of hydantoins

Journal Contribution - Journal Article

Subtitle:a novel class of potent antimycobacterial DprE1 inhibitors
Tuberculosis is the leading cause of death worldwide from infectious diseases. With the development of drug-resistant strains of Mycobacterium tuberculosis, there is an acute need for new medicines with novel modes of action. Herein, we report the discovery and profiling of a novel hydantoin-based family of antimycobacterial inhibitors of the decaprenylphospho-β-d-ribofuranose 2-oxidase (DprE1). In this study, we have prepared a library of more than a 100 compounds and evaluated them for their biological and physicochemical properties. The series is characterized by high enzymatic and whole-cell activity, low cytotoxicity, and a good overall physicochemical profile. In addition, we show that the series acts via reversible inhibition of the DprE1 enzyme. Overall, the novel compound family forms an attractive base for progression to further stages of optimization and may provide a promising drug candidate in the future.
Journal: Journal of medicinal chemistry
ISSN: 0022-2623
Volume: 61
Pages: 11221 - 11249
Publication year:2018
Keywords:A1 Journal article
BOF-keylabel:yes
BOF-publication weight:10
CSS-citation score:2
Authors:International
Authors from:Higher Education
Accessibility:Open