Repurposing Tolfenamic Acid, a Non-Steroidal Anti-Inflammatory Drug (NSAID), as an Antiplatelet Agent Targeting the P2Y12 Receptor
Year: 2025
Type: article
Abstract: The escalating burden of Ischaemic Heart Disease necessitates the unveiling of new avenues of therapy to improve the prognosis in affected patients. Drug repurposing is a very attractive approach in search of existing drugs with new indications. In this study, we have employed the ligand-based approach to drug repurposing in the search for potential candidates for ICH treatment, commencing from compounds already having evidence of clinical efficacy and mechanism of action. It was on this basis that Clopidogrel Bisulphate was adopted as the primary ligand in this study because it has a well-established mechanism of action and clinical application in preventing the formation of thrombus with an excellent safety profile. This foundation selection thus enabled the exploration of similar compounds that could possibly be repurposed for treating ICH.A ligand-based screening approach was conducted on the DrugRep platform for 20 compounds that bind to the target sites relevant to IHD treatment. This consisted of Clopidogrel, DB00758, by a binding score of 1.000; followed by antiplatelet agents such as Ticlopidine, 0.549; Prasugrel, 0.415; and Pizotifen, 0.341. Among the tested compounds, Indapamide (DB00808), Tolfenamic Acid (DB09216), and Ketotifen (DB00920) demonstrated tight binding at crucial receptor pockets, such as C2 and C5, which are very important for good drug binding and display of its therapeutic action in IHD.The molecular docking studies have derived that the binding affinity of Tolfenamic Acid was as high as -8.5 kcal/mol, showing great interaction with target pockets. Notably, in the active site of the receptor, Tolfenamic Acid interacts with the residues S101, N159, H187, and F252 through hydrogen bonds, hydrophobic contacts, and possible π-stacking interactions. All such noncovalent forces would contribute towards stabilizing and efficacy of ligand interaction with the receptor, thus making Tolfenamic Acid a good candidate for repurposing in the treatment of IHD.
Author: Kamble Shruti*, Khot Seema, Khamkar Sakshi, Udugade Vithal
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W6949199202
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