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 M (1), euphoscopin N (2) and euphornin L (3), and the lathyrane euphohelioscopin C (7) were isolated from plants of Euphorbia helioscopia L., together with four other known analogues, euphoscopin C (4), euphornin (5), epieuphoscopin B (6) and euphohelioscopin A (8). 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.
Barile
Elisa
E
DISTAAM, Università degli Studi del Molise, Via F. De Sanctis, I-86100 Campobasso, Italy.
Borriello
Marianna
M
Di Pietro
Attilio
A
Doreau
Agnès
A
Fattorusso
Caterina
C
Fattorusso
Ernesto
E
Lanzotti
Virginia
V
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry*; D000818:Animals; D004224:Diterpenes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D013237:Stereoisomerism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004224:Diterpenes; C530345:jatrophane; C530347:lathyrane