Amado Patrícia S M, Woodley Christopher, Cristiano Maria L S, O'Neill Paul M
Center of Marine Sciences - CCMAR, University of Algarve, P-8005-039 Faro, Portugal.
Department of Chemistry and Pharmacy, FCT, University of Algarve, P-8005-039 Faro, Portugal.
ACS Omega. 2022 Nov 3;7(45):40659-40681. doi: 10.1021/acsomega.2c05307. eCollection 2022 Nov 15.
Decaprenylphosphoryl-β-d-ribose 2'-epimerase (DprE1) is a critical flavoenzyme in , 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 .
癸异戊烯基磷酸化-β-D-核糖2'-表异构酶（DprE1）是结核分枝杆菌中的一种关键黄素酶，催化脂阿拉伯甘露聚糖和阿拉伯半乳聚糖生成过程中的一个关键步骤，这两种物质对于细胞壁生物合成均至关重要。由于其周质定位，DprE1是一个易受攻击的靶点，已经发现了几种具有不同骨架的化合物，它们可以共价或非共价方式抑制这种酶。我们通过对物理化学描述符以及吸收、分布、代谢、排泄和毒性（ADMET）进行深入分析，评估了2009年至2022年4月文献中公开的总共约1519种DprE1抑制剂，以深入了解这些DprE1抑制剂的这些特性。描述了几种有助于未来DprE1抑制剂设计和优化的分子特性，从而能够开发出针对结核分枝杆菌的改进类似物。
