Publication
Title
Identification and profiling of hydantoins : a novel class of potent antimycobacterial DprE1 inhibitors
Author
Abstract
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.
Language
English
Source (journal)
Journal of medicinal chemistry. - Washington, D.C., 1963, currens
Publication
Washington, D.C. : 2018
ISSN
0022-2623 [print]
1520-4804 [online]
Volume/pages
61:24(2018), p. 11221-11249
ISI
000454751100019
Pubmed ID
30500189
Full text (Publisher's DOI)
Full text (open access)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Project info
Medicinal chemistry open innovation doctorates (OpenMedChem).
Hit-to lead and lead optimization approaches in Mycobacterium tuberculosis drug-discovery.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 02.01.2019
Last edited 15.07.2021
To cite this reference