Identification of Novel Potential Herbal Drug Targets against Beta-Catenin in the Treatment of Oral Squamous Cell Carcinoma.

Abstract

Objective: The study aims to identify potential pharmacophore models for targeting beta-catenin, a crucial protein involved in the development of oral squamous cell carcinoma (OSCC), using a combination of herbal compounds and computational approaches.

Methods: Five natural compounds namely Quercetin, Lycopene, Ovatodiolide, Karsil, and Delphinidin were selected based on their reported activity against beta-catenin. Ligand characteristics were analyzed using SwissADME to evaluate drug-likeness, lipophilicity (logP), and bioavailability. The three-dimensional structure of beta-catenin was retrieved from the Protein Data Bank (PDB). Pharmacophore modeling was performed using Pharmagist software, followed by molecular docking using Swissdock to assess binding interactions and energies.

Results: Out of thousands of pharmacophore hits generated, 23 were selected based on drug-likeness properties. Molecular docking revealed that ZINC94512303, derived from the combination of the selected herbal compounds, exhibited the highest binding energy of -8.91 kcal/mol with beta-catenin, outperforming individual herbal compounds. This compound adhered to all drug-likeness rules and demonstrated optimal pharmacokinetic properties.

Conclusion: The identified pharmacophore, ZINC94512303, shows promise as a therapeutic agent targeting beta-catenin in OSCC. The combination of computational drug design with herbal compounds offers a novel approach to enhance the efficacy of cancer treatment. Further pharmacokinetic and pharmacodynamic studies, along with in vitro and clinical evaluations, are recommended to validate the therapeutic potential of this compound.