Volume 4 Number 1 2023
In Silico Drug-Likeness and Safety Profiling of Tinosporaside: A Natural Alternative to Celecoxib for COX-2 Inhibition
Md. Robiul Islam1*, Amena Khatun Manica2, Most Farhana Akter1, Md Abu Bakar Siddique3, Tufael4
Journal of Primeasia 4 (1) 1-8 https://doi.org/10.25163/primeasia.4110434
Submitted: 07 December 2022 Revised: 24 January 2023 Accepted: 27 January 2023 Published: 30 January 2023
Abstract
Background: Cyclooxygenase-2 (COX-2) is a key enzyme involved in the inflammatory response through the biosynthesis of prostaglandins from arachidonic acid. Although Celecoxib is a widely used COX-2 inhibitor, its long-term use has been associated with adverse effects including cardiovascular risk, hormonal imbalance, and general toxicity. Therefore, identifying a safer, naturally derived alternative is of growing importance in anti-inflammatory drug development.
Aim: This study aimed to investigate the potential of Tinosporaside, a glycosylated natural compound isolated from Tinospora cordifolia, as a safer and effective alternative to Celecoxib by evaluating its binding efficiency, toxicity, and pharmacokinetic behavior using in silico methods.
Methods: The crystal structure of COX-2 (PDB ID: 3LN1) was used for molecular docking with Celecoxib and Tinosporaside using AutoDock Vina within the PyRx platform. Ligands were geometrically optimized using Open Babel. Binding interactions were visualized with BIOVIA Discovery Studio. Pharmacokinetic and drug-likeness properties were assessed via SwissADME, while toxicity profiles were predicted using ProTox-II. A 100-nanosecond Molecular Dynamics (MD) simulation using GROMACS was performed to assess the structural stability and flexibility of ligand-protein complexes.
Results: Both ligands demonstrated strong binding affinity to the COX-2 active site. However, Tinosporaside exhibited a significantly lower predicted toxicity profile, high water solubility, and sustained interaction stability in MD simulations. Although it showed lower gastrointestinal absorption, its overall safety and binding behavior suggest therapeutic promise.
Conclusion: Tinosporaside shows promise as a safe, natural COX-2 inhibitor and may serve as an effective alternative to Celecoxib for long-term inflammation management.
Keywords: COX-2 inhibition, Tinosporaside, Celecoxib, Molecular docking, ADME profiling.
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