期刊
CURRENT ISSUES IN MOLECULAR BIOLOGY
卷 44, 期 7, 页码 2825-2841出版社
MDPI
DOI: 10.3390/cimb44070194
关键词
pharmacophore; structure-based drug design; NuBBE(DB); ADMET; molecular docking
资金
- Scientific Research Deanship at the University of Ha'il, Saudi Arabia [RG-20 137]
This study utilized a pharmacophore model and in silico filtering procedures to identify four potential ALR-2 inhibitors from a natural compound database. These compounds demonstrated increased binding affinity and more stable interactions.
Diabetic peripheral neuropathy (DPN) is a common diabetes complication (DM). Aldose reductase -2 (ALR-2) is an oxidoreductase enzyme that is most extensively studied therapeutic target for diabetes-related complications that can be inhibited by epalrestat, which has severe adverse effects; hence the discovery of potent natural inhibitors is desired. In response, a pharmacophore model based on the properties of eplarestat was generated. The specified pharmacophore model searched the NuBBE(DB) database of natural compounds for prospective lead candidates. To assess the drug-likeness and ADMET profile of the compounds, a series of in silico filtering procedures were applied. The compounds were then put through molecular docking and interaction analysis. In comparison to the reference drug, four compounds showed increased binding affinity and demonstrated critical residue interactions with greater stability and specificity. As a result, we have identified four potent inhibitors: ZINC000002895847, ZINC000002566593, ZINC000012447255, and ZINC000065074786, that could be used as pharmacological niches to develop novel ALR-2 inhibitors.
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