Bioinformatics-based discovery of a new norsesquiterpenoid from agarwood targeting CHRM2 and regulating the PI3K-Akt pathway in liver cancer

A novel norsesquiterpenoid isolated from agarwood, features a rare oxaspiro[4.5]decane structure. It selectively inhibits human liver cancer cell proliferation (SMMC-7721) with an IC 50 of 18.82 μM, while showing weaker effects on gastric and ovarian cancer cells. Network pharmacology and molecular docking identified muscarinic acetylcholine receptor M2 (CHRM2) as a target, suggesting compound 1 disrupts the PI3K-Akt pathway. ADMET predictions indicate favorable pharmacokinetics. These findings position compound 1 as a promising CHRM2 antagonist for liver cancer therapy, highlighting the potential of natural product-based drug discovery. • A new norsesquiterpenoid from agarwooda novel. • MD simulations refined from 60 ns to 2 µs. • A novel CHRM2 antagonist for liver cancer.