Computational Exploration of Anti-Alzheimer Potential of Flavonoids against Inducible Nitric Oxide Synthetase: An In-silico Molecular Docking and ADMET Analysis Approach

Abstract

Alzheimer’s disease (AD) is a formidable challenge in neurodegenerative disorders, marked by relentless cognitive decline, memory impairment, and a pervasive neuroinflammatory milieu. Recent scientific inquiries have unveiled a compelling link between the rampant overexpression of inducible nitric oxide synthetase (iNOS) and the intricate pathogenesis of AD. Within this context, flavonoids, a diverse class of polyphenolic compounds widely distributed in fruits & vegetables, have garnered substantial interest due to their recognized antioxidant and anti-inflammatory attributes. This research endeavor harnessed the power of cutting edge in-silico molecular docking techniques to embark on a compelling exploration. Specifically, we aimed to unravel the therapeutic potential of various flavonoids as putative inhibitors of iNOS, with the ultimate objective of combatting the insidious progression of AD. Our investigative odyssey unveiled promising outcomes. Molecular docking simulations illuminated the binding interactions between diverse flavonoids and the iNOS enzyme, offering insights into their potential inhibitory prowess. Among these flavonoids, a notable contender emerged, denoted as CHEMBL490697, which exhibited a remarkable negative binding affinity of -8.3 kcal/mol, demonstrating its strong attraction to the targeted protein. Furthermore, CHEMBL490697, admirably traversed the rigorous terrain of drug likeness parameters, underscoring its potential as a viable therapeutic candidate. In summation, this comprehensive investigation has illuminated the potential of CHEMBL490697 as a promising therapeutic agent with drug like properties, exemplified by its robust, stable, and tight binding to the iNOS enzyme. These findings present a compelling avenue for further research and development in the pursuit of best managements for AD.

Unlocking Therapeutic Potential: A Comprehensive Exploration of FDA-Approved Sirolimus similars for Perivascular Epithelioid Cell Tumor Treatment through Transcriptomic Insight, Structural Integration, and Drug-Drug Similarity Analysis with Cavity-Guided Blind Docking

“…Further analysis and experimental validation would be crucial to confirm the in silico predictions and assess the practical implications of these molecular interactions in a biological context. 13,14…”

In-silico Discovery of Potential Dengue Type 2 Virus NS1 Inhibitors: A Natural Ligand Zingerone-Derived 3-Point Pharmacophore Screening and Structure-Guided Blind Docking Study

“…The results were analyzed to identify ligand binding modes, interactions, and binding energies. [22][23] Top Candidates and Binding Pockets T he top ca nd id ates, i nclud i ng CH EM BL2110675, CHEMBL2057301, CHEMBL3545254, CHEMBL445472, CHEMBL1568698, CHEMBL408701, CHEMBL3545237, CHEMBL4297500, CHEMBL4594399, and CHEMBL4297253, exhibited favorable binding interactions within specific pockets (C3) of the DENV-2 NS1 structure. Notably, CHEMBL408701 (Taurolithocholic Acid) demonstrated a high pharmacophore score and a significant Vina score of -8.8, indicating robust interactions within the binding site.…”

In-silico Study of Epicathecin from Cinnamomum verum Against Insulin Receptor for Diabetes Mellitus

“…Increasing insulin production is required in order to bring blood sugar levels down. 6,7 Blood glucose normalization, concurrent disease management, and lifestyle modification are the current methods of treating type 2 diabetes. The first line of treatment for insulin resistance in the liver and peripheral tissues is metformin.…”