Comparison of the gastroprotective effect of a diterpene lactone isolated from Croton cajucara with its synthetic derivatives

The effect of three new derivatives from dehydrocrotonin (DHC—compound I) on gastric damage in different animal models including gastric ulceration induced by a necrotic agent and hypothermic restrained-stress was studied: compound II (produced by reducing the cyclohexenone moiety of DHC with NaBH 4); compound III (produced by reducing the carbonyls with LiAlH 4); and compound IV (produced by transforming the lactone moiety into an amide). Their structures were confirmed on the basis of chemical and physicochemical evidence. When previously administered (p.o.) at a dose of 100 mg/kg, compound II significantly ( P0.05). However, compound IV, in which the lactone moiety was changed into an amide, when administered at the same dose (100 mg/kg, p.o.), was more effective. The presence of a lactone moiety or Michael acceptor is probably essential for the anti-ulcerogenic effect of these compounds.