Department of Computer Science, Jamia Millia Islamia, New Delhi, 110025, India.
J Mol Model. 2021 Mar 25;27(4):114. doi: 10.1007/s00894-021-04736-x.
Ovarian cancer is one of the highly prominent gynecological malignancies after breast cancer. Although myriad literature is available, there is no specific biomarker available for the personalized treatment strategy. The unavailability of effective drug therapy for ovarian cancer calls for an urgent push in its development from the multidisciplinary scientific community. Indian Ayurvedic medicine pharmacology is widely appreciated and accepted for its immense healthcare benefits. Bioinformatics and cheminformatics approaches can be effectively used to screen phytochemicals present in the Indian Ayurvedic plants against ovarian cancer target receptors. Recent studies discern that POTE, a cancer-testis antigen (CTA) family, plays a crucial role in the proliferation and progression of cancers including ovarian cancer. Specifically, POTEE paralog has been observed to be hypermethylated in ovarian cancer. This study undertakes an in silico analysis of Indian Ayurvedic plants for their anticancer efficacy against ovarian cancer proliferation target receptor POTEE. Structures of 100 phytochemicals from 11 Ayurvedic plants were screened with ADME criteria, and qualified phytochemicals were subjected to molecular docking and interaction analysis. Only 6 phytochemicals having a high affinity to the target receptor (POTEE) were then subjected to an all-atom replica exchange molecular dynamics simulation for 50 ns. Binding affinities of 6 phytochemicals cedeodarin, deodarin, hematoxylin, matairesinol, quercetin, and taxifolin with POTEE were -8.1, -7.7, -7.7, -7.9, -8.0, and - 7.7 kcal/mol, respectively, and their RMSD were recorded as zero. This study concludes that phytochemicals present in Indian Ayurvedic plants namely Cedrus deodara and Asparagus racemosus possess inhibitory effects against ovarian cancer proliferation receptor POTEE.
卵巢癌是继乳腺癌之后高度突出的妇科恶性肿瘤之一。尽管有大量文献，但针对个性化治疗策略，尚无特定的生物标志物。由于缺乏有效的卵巢癌药物治疗方法，多学科科学界迫切需要推动其发展。印度阿育吠陀医学药理学因其巨大的医疗保健益处而广受赞赏和接受。生物信息学和化学信息学方法可有效地用于筛选印度阿育吠陀植物中的植物化学物质，以针对卵巢癌靶受体进行筛选。最近的研究表明，癌症睾丸抗原（CTA）家族中的 POTE 在包括卵巢癌在内的癌症的增殖和进展中起着关键作用。具体而言，已经观察到 POTEE paralog 在卵巢癌中被高度甲基化。本研究对印度阿育吠陀植物进行了计算机分析，以研究其对卵巢癌增殖靶受体 POTEE 的抗癌功效。根据 ADME 标准筛选了 11 种阿育吠陀植物的 100 种植物化学物质的结构，合格的植物化学物质进行了分子对接和相互作用分析。只有 6 种与靶受体（POTEE）具有高亲和力的植物化学物质随后被用于 50ns 的全原子复制交换分子动力学模拟。6 种植物化学物质 cedeodarin、deodarin、苏木素、matairesinol、槲皮素和 taxifolin 与 POTEE 的结合亲和力分别为-8.1、-7.7、-7.7、-7.9、-8.0 和-7.7 kcal/mol，其 RMSD 记录为零。本研究得出结论，印度阿育吠陀植物中存在的植物化学物质，如雪松和天门冬，对卵巢癌增殖受体 POTEE 具有抑制作用。
