Identification of Putative Plant-Based ALR-2 Inhibitors to Treat Diabetic Peripheral Neuropathy

• Published in: Current issues in molecular biology 2022-06, Vol.44 (7), p.2825-2841
• Main Authors: Saeed, Mohd, Tasleem, Munazzah, Shoib, Ambreen, Kausar, Mohd Adnan, Sulieman, Abdel Moneim E., Alabdallah, Nadiyah M., El Asmar, Zeina, Abdelgadir, Abdelmuhsin, Al-Shammary, Asma, Alam, Md Jahoor, Badroui, Riadh, Zahin, Maryam
• Format: Article
• Language: English
• Subjects: ADMET; molecular docking; NuBBEDB; pharmacophore; structure-based drug design
• ISSN: 1467-3045; 1467-3037; 1467-3045
• DOI: 10.3390/cimb44070194

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 NuBBEDB 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.