ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Network Pharmacology, Molecular Docking, MD Simulation, and ADMET Analysis of Triazole Derivatives Against Parkinson’s Disease

Sneha Wali, Pushpaveni Chakravarthi, Subhas S Karki, and Harshitha B. M

Department of Pharmaceutical Chemistry, KLE College of Pharmacy, Bengaluru, India

E-mail: pushpavenic@klepharmblr.org

Received: 13 February 2026  Accepted: 2 May 2026

Abstract:

Parkinson’s disease (PD) is a progressive neurodegenerative disorder lacking effective disease-modifying therapies. Targeting key signaling proteins involved in neuronal survival represents a promising therapeutic strategy. In this study, an integrated in silico approach was employed to identify potential triazole-based inhibitors targeting PIK3CA (p110α), a critical component of the PI3K signaling pathway implicated in PD pathogenesis. Network pharmacology analysis was used to identify PD-associated targets, followed by molecular docking of 74 triazole derivatives against PIK3CA. Several compounds exhibited strong binding affinities, with SAP30 and SAP27 emerging as top candidates, displaying binding scores of − 9.0 kcal/mol and − 8.9 kcal/mol, respectively, exceeding those of the co-crystal ligand and reference drug. Both compounds formed stable hydrogen bonding and hydrophobic interactions within the active site. SAP30 was further prioritized based on favorable drug-likeness and machine learning-based toxicity screening. Molecular dynamics (MD) simulations over 200 ns confirmed the structural stability of the SAP30–PIK3CA complex, supported by stable RMSD, RMSF, radius of gyration, and persistent protein–ligand interactions. MM/GBSA analysis revealed a highly favorable binding free energy (ΔG_bind ≈ − 75 kcal/mol), dominated by van der Waals and lipophilic contributions. Principal component and free energy landscape analyses indicated restricted collective motions and a thermodynamically stable binding state. Collectively, these findings suggest that SAP30 represents a promising triazole-based lead compound for further experimental validation in Parkinson’s disease therapy.

Keywords: Parkinson’s disease; Triazole derivatives; PIK3CA; Molecular dynamics simulation; Network pharmacology

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-026-05008-9

Chemical Papers 80 (9) 10327–10343 (2026)