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

TL;DR

This study combines QSAR, deep learning, network pharmacology, and molecular docking to predict and analyze the cytotoxic effects of Garcinia cowa xanthones on HeLa cancer cells, identifying key compounds and targets.

Contribution

It introduces a novel integrated approach using Graph Deep Learning and network pharmacology to evaluate bioactive compounds' anti-cancer potential.

Findings

Graph Attention Network achieved R2 of 0.98 in predicting pIC50.

Network pharmacology identified key compounds and protein targets.

Molecular docking suggested MTOR as a potential target for cytotoxicity.

Abstract

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.