Discovery of a new series of jatrophane and lathyrane diterpenes as potent and specific P-glycoprotein modulators

A new series of diterpenes, the jatrophanes euphoscopin, euphoscopin N and euphornin L, and the lathyrane euphohelioscopin C were isolated from plants of Euphorbia helioscopia L., together with four other known analogues, euphoscopin C , euphornin , epieuphoscopin B and euphohelioscopin A. The new compound stereostructures were elucidated by NMR analysis and computational data. The resulting isolated diterpenes were found to be potent inhibitors of P-glycoprotein (ABCB1), while showing an absence of significant activity against BCRP (ABCG2), despite the high substrate overlapping of these transporters, thus including them in the third-generation class of specific multidrug transporter modulators.