Recent Advances of DprE1 Inhibitors against Mycobacterium tuberculosis: Computational Analysis of Physicochemical and ADMET Properties

Amado, Patricia SM, Woodley, Christopher, Cristiano, Maria LS and O'Neill, Paul M ORCID: 0000-0003-4338-0317 (2022) Recent Advances of DprE1 Inhibitors against Mycobacterium tuberculosis: Computational Analysis of Physicochemical and ADMET Properties ACS OMEGA, 7 (45). pp. 40659-40681. ISSN 2470-1343, 2470-1343

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Abstract

Decaprenylphosphoryl-β-d-ribose 2'-epimerase (DprE1) is a critical flavoenzyme in Mycobacterium tuberculosis, catalyzing a vital step in the production of lipoarabinomannan and arabinogalactan, both of which are essential for cell wall biosynthesis. Due to its periplasmic localization, DprE1 is a susceptible target, and several compounds with diverse scaffolds have been discovered that inhibit this enzyme, covalently or noncovalently. We evaluated a total of ∼1519 DprE1 inhibitors disclosed in the literature from 2009 to April 2022 by performing an in-depth analysis of physicochemical descriptors and absorption, distribution, metabolism, excretion, and toxicity (ADMET), to gain new insights into these properties in DprE1 inhibitors. Several molecular properties that should facilitate the design and optimization of future DprE1 inhibitors are described, allowing for the development of improved analogues targeting M. tuberculosis.

Item Type:	Article
Uncontrolled Keywords:	3404 Medicinal and Biomolecular Chemistry, 34 Chemical Sciences, Biodefense, Tuberculosis, Orphan Drug, Infectious Diseases, Rare Diseases, Emerging Infectious Diseases
Depositing User:	Symplectic Admin
Date Deposited:	02 Dec 2022 11:20
Last Modified:	16 Jan 2026 10:11
DOI:	10.1021/acsomega.2c05307
Open Access URL:	https://doi.org/10.1021/acsomega.2c05307
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3166487
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