ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
This article is part of the Research TopicAdvances in Novel Pharmacotherapeutics and Drug Discovery: Computational, Experimental, Translational, and Clinical Models, Volume IIView all 14 articles
Computational-Experimental Integration Identifies Potent Carbohydrate-Hydrolyzing Enzyme Inhibitors from Nardostachys jatamansi: Molecular Docking, Dynamics and Pharmacokinetic Predictions
Provisionally accepted
- 1University of La Frontera, Temuco, Chile
- 2Bahauddin Zakariya University Institute of Computing, Multan, Pakistan
- 3Universidad de Concepcion, Concepción, Chile
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Background: Current α-glucosidase and α-amylase inhibitors demonstrate limited therapeutic efficacy and significant gastrointestinal side effects, necessitating identification of novel antidiabetic agents. This study employed integrated computational and experimental approaches to evaluate carbohydrate hydrolyzing enzyme inhibitory potential of Nardostachys jatamansi and its phytochemicals. Material & Methods: Plant extracts were evaluated through enzymatic assays against α-glucosidase and α-amylase. Virtual screening of 144 phytochemicals employed molecular docking, followed by molecular dynamics simulations (100 ns) and density functional theory calculations at B3LYP/6-311++G(d,p) level. ADMET profiling assessed drug-likeness potential. Results: N. jatamansi extract demonstrated superior enzyme inhibition compared to acarbose: IC₅₀ values of α-glucosidase 61.7± 3.9 μg/mL and α-amylase 81.3±4.7 μg/mL versus 132.6±7.8 μg/mL and 112.1±6.2 μg/mL respectively. Molecular docking identified Virolin with selective α-glucosidase affinity (-9.6 kcal/mol) and Nardostachysin showing high α-amylase binding (-9.5 kcal/mol). Molecular dynamics revealed Nardostachysin-α-amylase complex stability (ΔG = -158.51 kcal/mol) throughout simulation, while Virolin-α-glucosidase complex showed late-stage dissociation. DFT calculations revealed HOMO-LUMO gaps of 4.78 eV (Virolin) and 4.57 eV (Nardostachysin) with distinct dipole moments of 4.83 and 6.29 Debye respectively. ADMET analysis confirmed favorable drug-likeness with complete Lipinski compliance and zero PAINS alerts for both lead compounds. Conclusion: N. jatamansi extract demonstrated experimentally superior enzyme inhibition compared to acarbose, while computational analysis identified Virolin and Nardostachysin as promising drug candi-dates, establishing a validated integrative approach for accelerating natural product antidiabetic lead discovery.
Keywords: molecular docking, Density Functional Theory, enzyme inhibition, Natural Products, Molecular Dynamics Simulation, ADMET profiling, Antidiabetic agents, Nardostachys jatamansi
Received: 26 Sep 2025; Accepted: 12 Dec 2025.
Copyright: © 2025 Iqbal, Malik, Bernal, Salas-Burgos and Salazar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Luis A. Salazar
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