De novo in silico screening of natural products for antidiabetic drug discovery: ADMET profiling, molecular docking, and molecular dynamics simulations
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Date
2025-02-07
Journal Title
Journal ISSN
Volume Title
Publisher
Springer
Abstract
Epigenetic dysfunction which has implicated disease conditions such as diabetes highlights the urgency for the discovery
of novel therapeutic alternatives. The rising global incidences of diabetes and the limitations of existing treatments further
exacerbate the quest for novel antidiabetic agents’ discovery. This study leverages computational approaches to screen
selected bioactive natural product phytoconstituents for their potential anti-diabetic properties. Utilizing pharmaceutical
profiling, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) predictions, molecular docking, and
molecular dynamics (MD) simulations, the drug-likeness and binding affinity of these natural compounds against human
pancreatic amylase was investigated. Out of the total 24,316 ZINC compounds screened for their binding scores with
amylase, ZINC85593620, ZINC85593668, and ZINC85490447 came top. The compounds had higher binding scores
than the standards (acarbose and ranirestat) with ZINC85593620 having the highest docking score of−12.162 kcal/mol
and interacted with key amino acid residues such as TRP 59, ILE 148, and ASP 197. Further validation through MD
simulations reveals that all the compounds showed minimal fluctuations relative to the standards indicating strong and
stable binding interactions suggesting potential effective inhibition of the enzyme. ZINC85593620 and ZINC85593668
showed promising distribution and availability characteristics for amylase inhibition. Overall, the compounds displayed
potential amylase inhibition which underscores their use as promising natural products in developing new antidiabetic
drugs. Further experimental validations are recommended to offer a potential solution to the pressing need for safer and
more effective antidiabetic therapies.