Jatrophane diterpenoids with multidrug-resistance modulating activity from the latex of Euphorbia nicaeensis

Seven previously undescribed jatrophane diterpenoids, nicaeenin A–G, with eight known jatrophane diterpenoids, namely euphodendrophanes A–C, F, N, O, Q, S, were isolated from latex of Euphorbia nicaeensis collected in Serbia. The chemical structures of the compounds were determined by spectroscopic analysis including 1D and 2D NMR and HRESIMS experiments. All but one of the previously undescribed jatrophanes, showed significant potential to inhibit P-glycoprotein (P-gp) activity in two MDR cancer cells (NCI-H460/R and DLD1-TxR). The most powerful were nicaeenin F and nicaeenin G. Moreover nicaeenin G significantly stronger sensitized NCI-H460/R cells to DOX than Dex-VER. Chemical investigation of the latex from Euphorbia nicaeensis led to isolation of fifteen jatrophane diterpenoids including seven unreported. The previously undescribed compounds were evaluated for their MDR activity and jatrophane with the prolonged effect on P-gp inhibition significantly stronger sensitized NCI-H460/R cells to DOX than Dex-VER. [Display omitted] •Fifteen jatrophanes were isolated from the latex Euphorbia nicaeensis.•The chemical structures were elucidated by spectroscopic techniques.•The P-gp activities of seven previously undescribed jatrophanes have been assessed.