Undescribed cucurbitacin-type triterpenoids from the roots of Trichosanthes cucumeroides with antitumor effects, and their molecular docking studies.
Trichosanthes cucumeroides (Cucurbitaceae) is a rich source of cucurbitacin-type triterpenoids, known for their diverse pharmacological effects. This study aimed to isolate compounds from the roots of T. cucumeroides and to evaluate their cytotoxic activities and potential protein-binding interactions. The characterization of the isolated compounds was accomplished using spectroscopic and spectrometric approaches, including 1D/2D NMR, ECD, UV, IR, HR-ESI-MS, and X-ray crystallography. The antitumor effects were studied against different cell lines (MDA-MB-231, SKOV3, T24, and HUVEC) via MTT assays. Phytochemical investigation of T. cucumeroides yielded 25 compounds (1-25), including 11 undescribed kugualiansu A-K (1-11) and 14 known compounds (12-25). Additionally, the X-ray structures of compounds 2, 13, 17, and 20 were also reported. All compounds were assessed for cytotoxic activity against four cell lines, and their SARs were discussed. The MTT assay showed that some compounds exhibited significant effects with IC50 values from 0.051 to >20 μM. Moreover, compounds 19, 24, and 25 showed the most significant cytotoxicity against MDA-MB-231, SKOV3, and T24, with IC50 values of 0.098 ± 0.010, 0.054 ± 0.010, and 0.051 ± 0.010 μM, respectively. Furthermore, molecular docking studies were conducted for all compounds to analyze protein-ligand interactions and were supported by SPR and CETSA studies.