Profiling of euphane and tirucallane triterpenes from Euphorbia systyloides on antichagasic activity reveals antileukemia and immunomodulatory effects

Background Euphorbia is one of the largest genera in the spurge family and is rich in bioactive secondary metabolites, especially triterpenoids and diterpenoids. Euphorbia systyloides Pax. (Euphorbiaceae) is native to tropical Africa, and its leaf decoction has traditionally been used to treat tapeworm infections. Its chemistry has not been previously investigated.Objective This study aimed to investigate the terpenoid constituents of E. systyloides and evaluate the bioactivity of the compounds against Trypanosoma cruzi and tumor cells.Materials and methods Compounds were isolated by multistep chromatography and structurally elucidated using HRMS and 1D/2D NMR. Biological activity was assessed against T. cruzi epimastigotes (XTT assay), and host cell infection and amastigote replication assays, while cytotoxicity was evaluated in HL60, U937, and PBMCs (MTT assay). Immunomodulatory effects were assessed by ELISA measurement of TNF-α and IL-10 in infected macrophages.Results Six new euphane and tirucallane triterpenes and six known triterpenes were isolated. None were selectively active against T. cruzi. One ergostane triterpene exhibited nanomolar cytotoxicity against HL60 and U937 cell lines, with moderate toxicity toward PBMCs. Unexpectedly, kansenonol enhanced amastigote replication in host cells, likely through macrophage immunomodulation.Discussion and conclusions Our results indicate that the ergostane triterpene represents an unexplored scaffold for antileukemic drug discovery. Based on an unexpected observation in a cellular T. cruzi trypomastigote infection assay, kansenonol was found to exert significant immunomodulatory effects in vitro. Overall, this study shows that triterpenoids from E. systyloides primarily exert cytotoxic and immunomodulatory effects rather than selective antiparasitic activity.