In silico identification of chemical compounds in Spondias mombin targeting aldose reductase and glycogen synthase kinase 3β to abate diabetes mellitus

Ajiboye, B. O.; Fagbola, T. M.; Folorunso, I. M.; Salami, A. W.; Aletile, O. N.; Akomolede, B. A.; Ayemoni, F. I.; Akinfemiwa, K. I.; Anwo, V. O.; Ojeleke, M. I.; Oyinloye, B. E.

Abstract

Aldose reductase and glycogen synthase kinase 3β (GSK3β) represent two of the ideal drug targets in diabetes due to their role in the pathogenesis of diabetes. Studies have shown that plant compounds provide therapeutics in diabetes management. This study identified some compounds in S. mombin as dual inhibitors of aldose reductase and GSK3β. S. mombin compounds (n = 100) were docked with both aldose reductase and GSK3β; and the nine top scoring compounds were identified. The plant compounds were further investigated with MM-GBSA, ADME, HOMO/LUMO and constructed QSAR model to determine its stability with the targets, evaluate its drug-likeness, identify reactive molecules and predict its bioactivities against the proteins. The results show that the nine-top scoring compounds (Quercetin, Catechin, Ellagic acid, Tangeretin, Estradiol, Epicatechin, linalool, 2-Nitroethyl benzene, and Eugenol) attained stability with the proteins, and they also demonstrated excellent drug-like and pharmacokinetic characteristics, which qualifies them as drug candidates. The results identified linalool as the most reactive compound and Catechin as the most chemically inert molecules among the leads. The constructed QSAR model validated the molecular docking results by predicting satisfactory biological activities of the plant compounds against both targets. Although, the current findings have identified S. mombin compounds as dual inhibitors of aldose reductase and GSK3β, experimental studies are ongoing to validate the findings made by this study.

Citation

Ajiboye, B. O., Fagbola, T. M., Folorunso, I. M., Salami, A. W., Aletile, O. N., Akomolede, B. A., Ayemoni, F. I., Akinfemiwa, K. I., Anwo, V. O., Ojeleke, M. I., & Oyinloye, B. E. (2023). In silico identification of chemical compounds in Spondias mombin targeting aldose reductase and glycogen synthase kinase 3β to abate diabetes mellitus. Informatics in Medicine Unlocked, 36, Article 101126. https://doi.org/10.1016/j.imu.2022.101126

• Journal Article Type: Article
• Acceptance Date: Nov 1, 2022
• Online Publication Date: Nov 11, 2022
• Publication Date: Jan 1, 2023
• Deposit Date: Jan 28, 2024
• Publicly Available Date: Jan 29, 2024
• Journal: Informatics in Medicine Unlocked
• Print ISSN: 2352-9148
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 36
• Article Number: 101126
• DOI: https://doi.org/10.1016/j.imu.2022.101126
• Keywords: Diabetes; Aldose reductase; Glycogen synthase 3β; Molecular docking; Drug candidate; Drug discovery
• Public URL: https://hull-repository.worktribe.com/output/4161515