Ravindran Rekha, Sharma Nitika, Roy Sujata, Thakur Ashoke R, Ganesh Subhadra, Kumar Sriram, Devi Jamuna, Rajkumar Johanna
Department of Biotechnology, Rajalakshmi Engineering College, Chennai -602105, India.
Curr Comput Aided Drug Des. 2015;11(3):212-21. doi: 10.2174/1573409912666151106115848.
Withania somnifera commonly known as Ashwagandha in India is used in many herbal formulations to treat various cardiovascular diseases. The key metabolite of this plant, Withaferin A was analyzed for its molecular mechanism through docking studies on different targets of cardiovascular disease. Six receptor proteins associated with cardiovascular disease were selected and interaction studies were performed with Withaferin A using AutoDock Vina. CORINA was used to model the small molecules and HBAT to compute the hydrogen bonding. Among the six targets, β1- adrenergic receptors, HMG-CoA and Angiotensinogen-converting enzyme showed significant interaction with Withaferin A. Pharmacophore modeling was done using PharmaGist to understand the pharmacophoric potential of Withaferin A. Clustering of Withaferin A with different existing drug molecules for cardiovascular disease was performed with ChemMine based on structural similarity and physicochemical properties. The ability of natural active component, Withaferin A to interact with different receptors associated with cardiovascular disease was elucidated with various modeling techniques. These studies conclusively revealed Withaferin A as a potent lead compound against multiple targets associated with cardiovascular disease.
印度通常称为印度人参的睡茄被用于许多草药配方中，以治疗各种心血管疾病。通过对心血管疾病不同靶点的对接研究，分析了这种植物的关键代谢产物——睡茄素A的分子机制。选择了六种与心血管疾病相关的受体蛋白，并使用AutoDock Vina对睡茄素A进行相互作用研究。使用CORINA对小分子进行建模，并使用HBAT计算氢键。在这六个靶点中，β1-肾上腺素能受体、HMG-CoA和血管紧张素原转换酶与睡茄素A表现出显著相互作用。使用PharmaGist进行药效团建模，以了解睡茄素A的药效团潜力。基于结构相似性和物理化学性质，使用ChemMine对睡茄素A与不同的现有心血管疾病药物分子进行聚类。通过各种建模技术阐明了天然活性成分睡茄素A与心血管疾病相关不同受体相互作用的能力。这些研究最终揭示了睡茄素A是一种针对与心血管疾病相关的多个靶点的有效先导化合物。
