In Silico Analysis of Phytochemicals Targeting Key Proteins in Diabetes Mellitus - An Integrative Approach

Agastya Karthikeya Sivanandan, Vikas Jha

Abstract: Type 2 Diabetes Mellitus (T2DM) is a complex metabolic disorder requiring multi-target therapeutic strategies beyond conventional mono-target drugs. This study employed an integrative in silico approach to identify phytochemicals capable of simultaneously modulating key enzymes governing steroid metabolism, glucose sensing, and carbohydrate digestion. A curated set of antidiabetic phytochemicals was screened using SwissADME and ProTox-II to evaluate drug- likeness and toxicity. Molecular docking (AutoDock Vina) was performed against three critical T2DM-associated targets- 17β-Hydroxysteroid Dehydrogenase (1BHS), Glucokinase (1V4S), and Maltase-Glucoamylase (3CTT)- followed by interaction analysis using BIOVIA Discovery Studio. Silymarin, Procyanidin, (+)-Ursolic Acid, Anthocyanins, and Epicatechin showed strong multi-target binding. However, high-scoring polyphenols frequently violated Lipinski's rules and exhibited low predicted absorption. Epicatechin emerged as the most promising lead, combining balanced binding affinities (-7.8 to -8.8 kcal/mol) with full compliance to major drug-likeness filters, high gastrointestinal absorption, and the safest predicted toxicity profile (LD₅₀ > 2000 mg?kg^-1). Epicatechin's optimal ADME-toxicity profile and multitarget inhibitory potential highlight its strong translational promise. By modulating 17β-HSD, GCK, and MGA, it may simultaneously improve insulin sensitivity, enhance glucose phosphorylation, and reduce postprandial glucose spikes, supporting its potential application as a next-generation T2DM therapeutic candidate.

Keywords: Type 2 Diabetes Mellitus (T2DM), Phytochemicals, Molecular Docking, 17β-Hydroxysteroid Dehydrogenase, Glucokinase , Maltase-Glucoamylase

How to Cite?: Agastya Karthikeya Sivanandan, Vikas Jha, "In Silico Analysis of Phytochemicals Targeting Key Proteins in Diabetes Mellitus - An Integrative Approach", Volume 14 Issue 12, December 2025, International Journal of Science and Research (IJSR), Pages: 2159-2178, https://www.ijsr.net/getabstract.php?paperid=SR251222075739, DOI: https://dx.doi.org/10.21275/SR251222075739