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

被引：28

作者：

Amado, Patricia S. M. ^{[1
,2
,3
]}

Woodley, Christopher ^{[3
]}

Cristiano, Maria L. S. ^{[1
,2
]}

O'Neill, Paul M. ^{[3
]}

机构：

[1] Univ Algarve, Ctr Marine Sci CCMAR, P-8005039 Faro, Portugal

[2] Univ Algarve, Dept Chem & Pharm, FCT, P-8005039 Faro, Portugal

[3] Univ Liverpool, Dept Chem, Liverpool L69 7ZD, Lancs, England

来源：

ACS OMEGA | 2022年

关键词：

ASSAY INTERFERENCE COMPOUNDS; DRUG DISCOVERY; BENZOTHIAZINONE DERIVATIVES; IN-SILICO; ANTIMYCOBACTERIAL ACTIVITY; ANTITUBERCULAR EVALUATION; NONCOVALENT INHIBITORS; BIOLOGICAL EVALUATION; COMPOUNDS PAINS; SMALL-MOLECULE;

D O I：

10.1021/acsomega.2c05307

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

D e cap renylp ho sp ho ryl-beta-D-rib os e 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 similar to 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.

引用

页码：40659 / 40681

页数：23

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