Integrated untargeted metabolomics and bioactivity studies as new insights into the chemotaxonomy of Hura crepitans specimens from Peru and Sub-Saharan Africa

Hura crepitans (Euphorbiaceae), is widespread in the Amazon rainforest and on plantations in sub-Saharan Africa. This tree produces an irritating milky latex rich in secondary metabolites, notably daphnane-type diterpenes and cerebrosides. Previous studies have shown that huratoxin, the main daphnane in the latex, significantly and selectively inhibited the growth of colorectal cancer cells through a unique mechanism involving the activation of PKCζ. One major challenge in isolating active molecules from natural products is the accessibility of the resource. This study explores the phytochemical composition and cytotoxic activities of latexes collected in Peru, Benin, and Togo using UHPLC-MS and metabolomics tools to identify a renewable source of bioactive compounds. Significant inter- and intra-continental differences in chemical composition have been highlighted, with daphnanes being concentrated in the Peruvian samples. Extracts form latexes collected in Peru showed cytostatic activity on Caco-2 cells, correlated with the presence of daphnanes, while some African samples exhibited cytotoxic activity on Jurkat and Hela cancer cell lines, leading to the identification of potential other new bioactive compounds such as elasterol and cerebrosides. OBJECTIVE: To compare the composition of different Hura crepitans latex samples and determine their cytotoxic activity in order to identify new bioactive compounds CONCLUSIONS: Inter- and intra-continental variations in the phytochemical composition of latex were observed, leading to significant cytotoxic activities on different cell lines. Daphnanes were identified as responsible for the activity on Caco-2 cells, while elasterol and cerebrosides were putatively associated with the activity on Hela cells.