Department of Life Sciences, CHRIST (Deemed to Be University), Bangalore, India.
Laboratory of Advanced Cell Biology, Department of Botany, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, West Bengal, India, 700019.
Appl Biochem Biotechnol. 2022 Oct;194(10):4867-4891. doi: 10.1007/s12010-022-04006-3. Epub 2022 Jun 7.
Occurrence of cervical cancer, caused due to persistent human papilloma virus (HPV) infection, is common in women of developing countries. As the conventional treatments are expensive and associated with severe side effects, there is a need to find safer alternatives, which is affordable and less toxic to the healthy human cells. Present study aimed to evaluate the anti-HPV and apoptotic potential of four compounds from the greater cardamom (Amomum subulatum Roxb. var. Golsey), namely rhein, phytosphingosine, n-hexadecenoic acid and coronarin E. Their anti-HPV and apoptotic potential were studied against viral E6, E7 and few anti-apoptotic proteins of host cell (BCL2, XIAP, LIVIN) by in silico docking technique. Phytochemicals from the plant extract were analysed and identified by LC/MS and GC/MS. Involvement of the target proteins in various biological pathways was determined through KEGG. Structural optimization of the three-dimensional structures of the ligands (four phytochemicals and control drug) was done by Avogadro1.1. Receptor protein models were built using ProMod3 and other advanced tools. Pharmacophore modelling of the selected phytochemicals was performed in ZINCPharmer. Swiss ADME studies were undertaken to determine drug likeness. The ligands and proteins were digitally docked in DockThor docking program. Protein flexibility-molecular dynamic simulation helped to study protein-ligand stability in real time. Finally, the correlation of evaluated molecules was studied by the use of principal component analysis (PCA) based on the docking scores. All the ligands were found to possess apoptotic and anti-cancer activities and did not violate Lipinsky criteria. n-Hexadecanoic acid and its analogues showed maximum efficacy against the target proteins. All the protein-ligand interactions were found to be stable. The uncommon phytochemicals identified from rhizomes of greater cardamom have anti-cancer, apoptotic and HPV inhibitory potentials as analysed by docking and other in silico studies, which can be utilized in drug development after proper experimental validation.
宫颈癌的发生是由于持续性人乳头瘤病毒(HPV)感染引起的,在发展中国家的女性中较为常见。由于传统的治疗方法昂贵且副作用严重,因此需要寻找更安全的替代品,这种替代品既经济实惠,又对健康细胞的毒性较小。本研究旨在评估来自大豆蔻(Amomum subulatum Roxb. var. Golsey)的四种化合物(大黄酸、植物鞘氨醇、正十六碳烯酸和 coronarin E)的抗 HPV 和促凋亡作用。通过计算机对接技术研究了它们对病毒 E6、E7 和宿主细胞几种抗凋亡蛋白(BCL2、XIAP、LIVIN)的抗 HPV 和促凋亡作用。通过 LC/MS 和 GC/MS 分析和鉴定植物提取物中的植物化学物质。通过 KEGG 确定了靶蛋白在各种生物途径中的作用。通过 Avogadro1.1 对配体(四种植物化学物质和对照药物)的三维结构进行了结构优化。使用 ProMod3 和其他先进工具构建了受体蛋白模型。在 ZINCPharmer 中对选定的植物化学物质进行了药效团建模。进行了瑞士 ADME 研究以确定药物相似性。在 DockThor 对接程序中对配体和蛋白质进行了数字化对接。蛋白质柔性-分子动力学模拟有助于实时研究蛋白质-配体的稳定性。最后,通过基于对接评分的主成分分析(PCA)研究了评估分子的相关性。所有配体均具有促凋亡和抗癌活性,且不违反 Lipinski 准则。正十六碳烯酸及其类似物对靶蛋白显示出最大的功效。所有的蛋白-配体相互作用都被发现是稳定的。通过对接和其他计算机模拟研究,从大豆蔻根茎中鉴定出的不常见植物化学物质具有抗癌、促凋亡和抑制 HPV 的潜力,在经过适当的实验验证后,可用于药物开发。