Snehalatha A V, Kumar N V Anil
Department of Chemistry, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, Udupi 576104, Karnataka, India.
Scientifica (Cairo). 2025 Jul 9;2025:2105236. doi: 10.1155/sci5/2105236. eCollection 2025.
This study aimed to investigate the potential of natural products (NPs) as inhibitors of decaprenylphosphoryl-D-ribose 2'-epimerase (DprE1), an enzyme crucial in cell wall synthesis. Over 100 NPs were screened for anti-TB properties. Subsequently, the binding mechanism of the most potent inhibitor to DprE1 was investigated using computational methods, including molecular docking and simulations. Three compounds (CNP0123918, CNP0041612, and CNP0281145) were identified with promising binding interactions within DprE1's active site. CNP0123918 emerged as the top candidate, exhibiting good interaction with key residues in DprE1. This study suggests that computer-aided drug repurposing holds potential as a successful strategy for identifying novel anti-TB drugs. These findings contribute to the development of novel DprE1 inhibitors. Future research will focus on in vitro assays and in vivo and toxicology assessment of CNP0123908 to establish its potential as an effective DprE1 inhibitor.
本研究旨在探究天然产物作为去甲戊二烯基磷酸化-D-核糖2'-表异构酶（DprE1）抑制剂的潜力，DprE1是一种在细胞壁合成中起关键作用的酶。对100多种天然产物进行了抗结核特性筛选。随后，使用包括分子对接和模拟在内的计算方法研究了最有效抑制剂与DprE1的结合机制。鉴定出三种化合物（CNP0123918、CNP0041612和CNP0281145）在DprE1活性位点内具有良好的结合相互作用。CNP0123918成为首选候选物，与DprE1中的关键残基表现出良好的相互作用。本研究表明，计算机辅助药物重新利用作为一种成功的策略，在识别新型抗结核药物方面具有潜力。这些发现有助于新型DprE1抑制剂的开发。未来的研究将集中于对CNP0123908进行体外试验以及体内和毒理学评估，以确定其作为有效DprE1抑制剂的潜力。
