Computational Chemistry Group (CCG), Amrita School of Engineering, Amrita Vishwa Vidyapeetham, Coimbatore 641112, India.
Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences, Nitte (Deemed to be University), Deralakatte, Mangaluru 575018, India.
Medicina (Kaunas). 2023 Aug 2;59(8):1412. doi: 10.3390/medicina59081412.
Breast cancer is a significant type of cancer among women worldwide. Studies have reported the anti-carcinogenic activity of Hydrastis Canadensis (Goldenseal) in cancer cell lines. Hydrastis Canadensis could help eliminate toxic substances due to its anti-cancer, anti-inflammatory, and other properties. The design phase includes the identification of potential and effective molecules through modern computational techniques. Objective: This work aims to study Hydrastis Canadensis's effect in controlling hormone-independent breast cancer through in-silico analysis. The preliminary screening of reported phytochemicals includes biomolecular networking. Identifying functionally relevant phytochemicals and the respective target mutations/genes leads to selecting 3D proteins of the desired mutations being considered the target. Interaction studies have been conducted using docking. The kinetic and thermodynamic stability of complexes was studied through molecular dynamic simulation and MM-PBSA/GBSA analysis. Pharmacodynamic and pharmacokinetic features have been predicted. The mechanism-wise screening, functional enrichment, and interactional studies suggest that canadaline and Riboflavin effectively interact with the target proteins. Hydrastis Canadensis has been identified as the effective formulation containing all these constituents. The phytoconstituents; Riboflavin and Canadensis showed good interaction with the targets of hormone-independent breast cancer. The complexes were found to be kinetically and thermodynamically stable. Hydrastis Canadensis has been identified as effective in controlling 'hormone-independent or basal-like breast cancer' followed by 'hormone-dependent breast cancer: Luminal A' and Luminal B.
乳腺癌是全球女性中一种重要的癌症类型。研究报告称，白头翁（白毛茛）具有抗癌活性，可以帮助消除因癌症、炎症等特性而产生的有毒物质。设计阶段包括通过现代计算技术识别潜在的有效分子。目的：本工作旨在通过计算机分析研究白头翁对激素非依赖性乳腺癌的控制作用。对报告的植物化学物质进行初步筛选，包括生物分子网络。鉴定具有功能相关性的植物化学物质和相应的靶基因突变/基因，从而选择考虑为靶标的所需突变的 3D 蛋白质。通过对接进行相互作用研究。通过分子动力学模拟和 MM-PBSA/GBSA 分析研究复合物的动力学和热力学稳定性。预测了药效动力学和药代动力学特征。基于机制的筛选、功能富集和相互作用研究表明，白头翁碱和核黄素能有效地与靶蛋白相互作用。白头翁被确定为含有所有这些成分的有效配方。植物化学物质；核黄素和白头翁与激素非依赖性乳腺癌的靶标表现出良好的相互作用。复合物被发现具有动力学和热力学稳定性。白头翁被确定为有效控制“激素非依赖性或基底样乳腺癌”，其次是“激素依赖性乳腺癌：Luminal A”和 Luminal B。
