用图神经网络预测藤黄属黄酮类化合物对宫颈癌细胞的毒性，发现关键靶点。
In silico study on the cytotoxicity against Hela cancer cells of xanthones bioactive compounds from Garcinia cowa: QSAR based on Graph Deep Learning, Network Pharmacology, and Molecular Docking
- 基于图注意力网络预测黄酮类化合物毒性，准确率高
- 发现MTOR是诱导宫颈癌细胞毒性的潜在靶点
- 适合药物研发与天然产物抗癌机制研究者
癌症是一组复杂的疾病，全球死亡率最高，且患病率上升，发病年龄趋于年轻化。其特征为异常细胞不受控制地增殖、侵袭邻近组织并转移至远端器官。藤黄属植物Garcinia cowa广泛用于东南亚传统医药，如越南，用于治疗发热、咳嗽、消化不良、通便及寄生虫病。该植物中分离出的多种黄酮类化合物具有广泛的生物活性，部分显示出抗肿瘤和抗疟潜力。网络药理学分析成功识别出关键活性成分Rubraxanthone、Garcinone D、Norcowanin、Cowanol和Cowaxanthone，及其主要蛋白靶点TNF、CTNNB1、SRC、NFKB1和MTOR，揭示了其抗肿瘤作用的分子机制。图注意力网络算法表现出优异预测性能，在数据增强后达到R²=0.98，RMSE=0.02，显著提升对黄酮类化合物pIC50值的预测精度。此外，分子对接结果显示MTOR可能是诱导HeLa癌细胞毒性的潜在靶点。
原文摘要 · Abstract (English)
Cancer is recognized as a complex group of diseases, contributing to the highest global mortality rates, with increasing prevalence and a trend toward affecting younger populations. It is characterized by uncontrolled proliferation of abnormal cells, invasion of adjacent tissues, and metastasis to distant organs. Garcinia cowa, a traditional medicinal plant widely used in Southeast Asia, including Vietnam, is employed to treat fever, cough, indigestion, as a laxative, and for parasitic diseases. Numerous xanthone compounds isolated from this species exhibit a broad spectrum of biological activities, with some showing promise as anti cancer and antimalarial agents. Network pharmacology analysis successfully identified key bioactive compounds Rubraxanthone, Garcinone D, Norcowanin, Cowanol, and Cowaxanthone alongside their primary protein targets (TNF, CTNNB1, SRC, NFKB1, and MTOR), providing critical insights into the molecular mechanisms underlying their anti-cancer effects. The Graph Attention Network algorithm demonstrated superior predictive performance, achieving an R2 of 0.98 and an RMSE of 0.02 after data augmentation, highlighting its accuracy in predicting pIC50 values for xanthone based compounds. Additionally, molecular docking revealed MTOR as a potential target for inducing cytotoxicity in HeLa cancer cells from Garcinia cowa.
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