评估[植物名称]中的植物化学物质对 NAD[P]H-醌氧化还原酶的抗癌活性。

evaluations of phytochemicals from exhibiting anticancer activity against NAD[P]H-quinone oxidoreductase.

机构信息

Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru, India.

Department of Bioinformatics, University of Potsdam, Potsdam, Germany.

出版信息

Hum Exp Toxicol. 2024 Jan-Dec;43:9603271241291399. doi: 10.1177/09603271241291399.

DOI:10.1177/09603271241291399

PMID:39397382

Abstract

BACKGROUND

Cancer is a leading cause of death globally and in the US, prompting research into medicinal plants with anticancer properties. , or Ashwagandha, is one such plants, known for its diverse pharmacological effects. Withaferin A and Viscosalactone B are two compounds found in Ashwagandha with known anticancer activity. The protein NQO1, overexpressed in various cancers, was the focus of this study.

HYPOTHESIS AND AIM

We hypothesize that specific phytochemicals in can effectively interact with and inhibit the NQO1 protein, thereby exhibiting anticancer properties. This study aims to identify these interactions using in silico approaches.

METHODOLOGY

CFDT was performed using the Gaussian 16 program package, followed by QSAR analysis of the compounds in the PASS online web server. The Schrodinger suite was used to carry out ligand and protein preparation, molecular docking, and molecular dynamic simulation to analyse the interaction of these compounds with NQO1 and ADME studies. Protox-II and SWISSADME tools were used to predict the toxicity and blood-brain barrier permeability of the phytochemicals.

RESULTS AND CONCLUSION

CDFT and frontier molecular orbital analyses predicted the stability and reactivity of all the selected molecules. QSAR analysis predicted the biological activity and toxicity of the compounds. Withaferin A exhibited the highest glide gscore (-4.953 kcal/mol) and demonstrated 6 hydrogen bond interactions with NQO1, suggesting its potential as an anticancer agent. Conceptual density functional theory-based analysis suggested the strong electrophilicity of the ligands, further supporting their potential anticancer activities. Viscosalactone B, another phytochemical from Ashwagandha, also showed interactions involving 6 hydrogen bonds with NQO1, with a glide gscore of (-4.593 kcal/mol). Molecular dynamic simulations validated the stability of the Withaferin A-NQO1 complex. ADME-T properties predicted high oral absorption for the selected ligands, indicating that Withaferin A could be a viable orally administered drug.

摘要

背景

癌症是全球和美国的主要死亡原因，促使人们对具有抗癌特性的药用植物进行研究。印度人参，也被称为 Ashwagandha，就是这样一种植物，具有多种药理学作用。Withaferin A 和 Viscosalactone B 是印度人参中两种具有已知抗癌活性的化合物。本研究的重点是蛋白 NQO1，它在各种癌症中过表达。

假设和目的

我们假设印度人参中的特定植物化学物质可以有效地与 NQO1 蛋白相互作用并抑制其活性，从而表现出抗癌特性。本研究旨在使用计算方法来确定这些相互作用。

方法

使用 Gaussian 16 程序包进行 CFDT，然后在 PASS 在线网络服务器上对化合物进行 QSAR 分析。使用 Schrodinger 套件进行配体和蛋白质准备、分子对接和分子动力学模拟，以分析这些化合物与 NQO1 的相互作用，并进行 ADME 研究。使用 Protox-II 和 SWISSADME 工具预测植物化学物质的毒性和血脑屏障通透性。

结果和结论

CDFT 和前沿分子轨道分析预测了所有选定分子的稳定性和反应性。QSAR 分析预测了化合物的生物活性和毒性。Withaferin A 表现出最高的 Glide gscore（-4.953 kcal/mol），并与 NQO1 发生 6 个氢键相互作用，表明其作为抗癌剂的潜力。基于概念密度泛函理论的分析表明配体具有很强的亲电性，进一步支持其潜在的抗癌活性。印度人参中的另一种植物化学物质 Viscosalactone B 也与 NQO1 发生涉及 6 个氢键的相互作用，Glide gscore 为（-4.593 kcal/mol）。分子动力学模拟验证了 Withaferin A-NQO1 复合物的稳定性。ADME-T 特性预测所选配体具有高口服吸收性，表明 Withaferin A 可能是一种可行的口服药物。