C ucumis melo compounds: A new avenue for ALR-2 inhibition in diabetes mellitus

• Published in: Heliyon Vol. 10; no. 15; p. e35255
• Main Authors: Alshaghdali, Khalid, Tasleem, Munazzah, Rezgui, Raja, Alharazi, Talal, Acar, Tolgahan, Aljerwan, Raed Fahad, Altayyar, Ahmed, Siddiqui, Samra, Saeed, Mohd, Yadav, Dharmendra Kumar, Saeed, Amir
• Format: Journal Article
• Language: English
• Published: England 15.08.2024
• Subjects: MD simulation; Docking; Aldose reductase (ALR2); Cucumis melo; ADMET
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2024.e35255

Diabetes mellitus (DM) is a prominent contributor to morbidity and mortality in developed nations, primarily attributable to vascular complications such as atherothrombosis occurring in the coronary arteries. Aldose reductase (ALR2), the main enzyme in the polyol pathway, catalyzes the conversion of glucose to sorbitol, leading to a significant buildup of reactive oxygen species in different tissues. It is therefore a prime candidate for therapeutic targeting, and extensive study is currently underway to discover novel natural compounds that can inhibit it. has a long history as a lipid-lowering ethanopharmaceutical plant. In this study, compounds derived from were computationally evaluated as possible lead candidates. Various computational filtering methods were employed to assess the drug-like properties and ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiles of the compounds. The compounds were subsequently addressed to analysis of their interactions, molecular docking, and molecular dynamics simulation studies. When compared to the conventional therapeutic compounds, three compounds exhibited enhanced binding affinity and intra-molecular residue interactions, resulting in increased stability and specificity. Consequently, four potent inhibitors, namely PubChem CIDs 119205, 65373, 6184, and 332427, have been identified. These inhibitors exhibit promising potential as pharmacological targets for the advancement of novel ALR-2 inhibitors.