Exploration of leads from bis-indole based triazine derivatives targeting human aldose reductase in diabetic type 2: In-silico approaches

Roney, Miah and Issahaku, Abdul Rashid and Mohammed Nazim, Uddin and Wilhelm, Anke and Mohd Fadhlizil Fasihi, Mohd Aluwi (2025) Exploration of leads from bis-indole based triazine derivatives targeting human aldose reductase in diabetic type 2: In-silico approaches. 3 Biotech, 15 (5). pp. 1-16. ISSN 2190-572X. (Published)

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DOI/Official URL: https://doi.org/10.1007/s13205-024-04178-1

Abstract

Diabetes mellitus (DM) poses a major global healthcare challenge, highlighting the need for new treatments beyond current options. Currently available drugs have side effects including weight gain, nausea, vomiting, diarrhea, insulin resistance etc. Therefore, given the benefits of indole derivatives in diabetes and the lack of computational studies on bis-indole-based triazine derivatives with aldose reductase (AR), this study employs in-silico analysis to explore their potential as type-2 diabetes treatments. Based on the Differential Expression analysis, the human aldose reductase (HAR) encoding gene AKR1B1 showed overexpression in GSE30122 diabetes patients (Log2FC = 0.62, P < 0.01). Moreover, the compounds 2-((5,6-di(1H-indol-3-yl)-1,2,4-triazin-3-yl)thio)-1-(3-hydroxy-5-methylphenyl)ethan-1-one (4) and 2-((5,6-di(1H-indol-3-yl)-1,2,4-triazin-3-yl)thio)-1-(4-nitrophenyl)ethan-1-one (8) were identified as leading candidates, showing binding energies of − 62.12, − 81.73 kcal/mol and − 57.19, − 85.97 kcal/mol, respectively. Docking, MM/GBSA screening, molecular dynamics (MD) simulations, PCA, and post-MM/GBSA analysis confirmed their stability and favorable binding compared to the apo protein and control. Further in-vitro, in-vivo, and clinical studies are required to validate their therapeutic potential.

Item Type:	Article
Additional Information:	Indexed by Scopus
Uncontrolled Keywords:	Anti-diabetic; Bis-indole based triazine derivatives; Docking; Human aldose reductase; In-silico; MD Simulation
Subjects:	H Social Sciences > HD Industries. Land use. Labor Q Science > Q Science (General) T Technology > T Technology (General)
Faculty/Division:	Institute of Postgraduate Studies Faculty of Mechanical and Automotive Engineering Technology
Depositing User:	Mr Muhamad Firdaus Janih@Jaini
Date Deposited:	20 Feb 2025 05:04
Last Modified:	20 Feb 2025 05:04
URI:	http://umpir.ump.edu.my/id/eprint/43872
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