R Priyadarshini, Ramasubramanian Abilasha, Ramani Pratibha, Doble Mukesh
Department of Oral Pathology and Microbiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
Asian Pac J Cancer Prev. 2024 Dec 1;25(12):4181-4188. doi: 10.31557/APJCP.2024.25.12.4181.
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.
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.
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.
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.
本研究旨在结合草药化合物和计算方法，确定针对β-连环蛋白的潜在药效团模型，β-连环蛋白是参与口腔鳞状细胞癌（OSCC）发展的关键蛋白。
基于已报道的对β-连环蛋白的活性，选择了五种天然化合物，即槲皮素、番茄红素、卵叶二萜内酯、卡尔西尔和飞燕草素。使用SwissADME分析配体特征，以评估药物相似性、亲脂性（logP）和生物利用度。从蛋白质数据库（PDB）中检索β-连环蛋白的三维结构。使用Pharmagist软件进行药效团建模，随后使用Swissdock进行分子对接，以评估结合相互作用和能量。
在生成的数千个药效团命中物中，根据药物相似性属性选择了23个。分子对接显示，源自所选草药化合物组合的ZINC94512303与β-连环蛋白的结合能最高，为-8.91千卡/摩尔，优于单个草药化合物。该化合物符合所有药物相似性规则，并表现出最佳的药代动力学性质。
鉴定出的药效团ZINC94512303有望作为OSCC中靶向β-连环蛋白的治疗剂。计算药物设计与草药化合物的结合提供了一种提高癌症治疗疗效的新方法。建议进一步进行药代动力学和药效学研究，以及体外和临床评估，以验证该化合物的治疗潜力。
