A novel monoterpene indole alkaloid from Uncaria sessilifructus Roxb. and its antitumor activity and action mechanism

Uncaria sessilifructus Roxb. (U. sessilifructus) remains largely unexplored in chemical constituents and antitumor bioactivities. Ten compounds were isolated and structurally elucidated from the hooked stems and branches of U. sessilifructus. Herein, a novel compound 1 was identified through various spectroscopic analyses. In vitro antitumor assays revealed that compound 1 exhibited broad-spectrum antiproliferative activity against six tumour cell lines, with potent efficacy against HL-60 (IC₅₀ = 8.21 μM) and HeLa (IC₅₀ = 9.04 μM) cells, while showing low cytotoxicity towards L02 human normal liver cells (IC₅₀ > 40 μM). Network pharmacology analysis revealed that the enriched signalling pathways of compound 1 are mainly the MAPK and PI3K-AKT pathways, closely associated with the progression of leukaemia and cervical cancer. Molecular docking confirmed the stable binding of compound 1 to B-cell lymphoma 2 (BCL-2) and mitogen-activated protein kinase kinase 1 (MAP2K1) with binding free energies of -8.9 kcal mol^-1 and -9.6 kcal mol^-1, respectively. Overall, these results elucidate the dual antitumor mechanisms of compound 1, demonstrating its potential as a lead candidate for treating leukaemia and cervical cancer.