Sesquiterpenoids isolated from the rhizome of Valeton: antitumor activity, molecular docking and molecular dynamics study

Three undescribed sesquiterpenoids, phaeocaulisguatriol ( 1 ) and phaeocaulistriol A-B ( 19 , 20 ), along with twenty known sesquiterpenoids were isolated from a chloroform-soluble extract of Curcuma phaeocaulis Valeton rhizome. Their structures were determined using comprehensive spectroscopic methods. All isolated compounds were evaluated for their cytotoxicity against five human tumor cell lines Hela, HepG2, MCF-7, BGC823, and A549. Among them, phaeocaulisguatriol ( 1 ) and phaeocaulistriol B ( 20 ) showed potent cytotoxic activity against MCF-7 (IC 50 of 40.7 and 58.8 μM, respectively), by inducing apoptosis. The effectiveness of compounds 1 and 20 was supported by predictive intermolecular interactions in molecular docking. Molecular dynamics simulation studies further probed the interaction mechanism under simulated physiological conditions between the two most active compounds and the TP53 protein, an apoptotic effector protein. Moreover, Western blot experiments confirmed that compound 1 induces apoptosis by activating the expression of TP53 and caspase 3 proteins. This work provides a deep insight into new sesquiterpenoids isolated from C. phaeocaulis Valeton acting as potential antitumor activity inhibitors. This work provides a deep insight into new sesquiterpenoids isolated from Curcumae Rhizoma acting as potential antitumor activity inhibitors.