Belonging to the Euphorbiaceae family, the Jatropha genus is a promising source for the discovery of antitumor compounds. Jatropha ribifolia is a traditionally used species in folk medicine in the semi-arid region of Brazil, with a few chemical and pharmacological reports. Based on that, the aim of the current work is to isolate, structurally characterize, and assess the cytotoxic activity of isolated compounds through in vitro and in silico analyses. To achieve these main goals, the underground parts were dried, extracted and purified using classical and instrumental chromatographic techniques, leading to the isolation of 16 compounds. Altogether with HR-ESI-MS, IR, one- and two-dimensional NMR experiments, eight previously unreported diterpenes, named ribifolones A-H, along with eight known compounds, were obtained and are herein described. Regarding their activity against melanoma (SK-MEL-28) and colorectal cancer (HCT-116) cell lines, jatrophone was the most potent with IC50 values of 6.19 µM and 10.09 µM, followed by ribifolone C that exhibited a moderate cytotoxicity with IC50 values of 50.71 µM and 33.39 µM, respectively. Network pharmacology analysis suggests the involvement of the PI3K-AKT-mTOR pathway in the activity of both compounds; meanwhile, molecular docking and dynamics simulations demonstrate the main interactions with key proteins in the pathway, indicating putative targets. This work opens new perspectives for the discovery of bioactive compounds found in Euphorbiaceae species, especially from those occurring in Caatinga.
Souza et al. (Thu,) studied this question.