World Journal of
Pharmaceutical and Life Sciences

IN SILICO MOLECULAR DOCKING STUDIES AND ADMET SCREENING OF THE PHYTOCONSTITUENTS URS-12-ENE AND NEOPHYTADIENE AS POTENTIAL ANTIDIABETIC AGENTS

M. Muthazhagi, P. Muthulakshmi, N. Nandhini, S. Narmatha, R. Naveen, R. Nirmala*

ABSTRACT

Diabetes mellitus is a chronic metabolic disorder of global concern, with the number of affected individuals projected to rise from 590 million in 2025 to 853 million by 2050. Plant-derived phytoconstituents represent an attractive source of novel antidiabetic leads owing to their structural diversity and favourable safety profiles. In the present study, the binding interactions of two phytoconstituents, Urs-12-ene and Neophytadiene, were evaluated against two diabetes-associated targets, Glycogen Synthase Kinase-3 beta (GSK3-β; PDB ID: 7B6F) and Cholinesterase (PDB ID: 6QAB), using AutoDock Vina integrated within PyRx. Post-docking interaction analysis was carried out using BIOVIA Discovery Studio Visualizer, and drug-likeness and toxicity were predicted using SwissADME and pkCSM-based ADMET parameters. Urs-12-ene exhibited markedly stronger binding affinities than Neophytadiene against both targets, recording −8.1 kcal/mol against GSK3-β and −11.2 kcal/mol against cholinesterase, compared with −6.1 and −6.0 kcal/mol respectively for Neophytadiene. Both compounds satisfied most Lipinski drug-likeness criteria with a single lipophilicity violation and a bioavailability score of 0.55. Toxicity profiling revealed that Urs-12-ene was devoid of AMES mutagenicity, hepatotoxicity, hERG inhibition and skin sensitisation, whereas Neophytadiene showed predicted hERG II inhibition and skin sensitisation potential. These findings indicate that Urs-12-ene possesses favourable binding affinity, drug-likeness and safety characteristics, supporting its candidacy as a lead phytoconstituent for further antidiabetic drug development, pending experimental validation.

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