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 spectro-scopic 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-H460/12 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. (C) 2018 Elsevier Ltd. All rights reserved.