Jatrophanes as promising multidrug resistance modulators: Advances of structure-activity relationships

The phytochemical study of Euphorbia helioscopia afforded euphornin (1) in a large amount. Alkaline hydrolysis of 1 using potassium carbonate yielded the main product monodeacetyleuphornin (2), whose structural modification at 14-OH gave rise to 21 acylated derivatives euphornoate A-U (3-23). Thus, a mini compound library of jatrophanes was established to screen for MDR modulators. Biological studies clearly demonstrated the effect of C-14 pattern modification in MDR reversal activity and several compounds with RF values over 300 fold at 20 mu m (6, 16, 20, 22, 23) were thought to be promising MDR modulators. The SARs are discussed, which reveal that introduction of an alkyl acyl group bearing 4 carbons at C-14 or an aryl acyl group with electron donating groups is favorable for the activity.