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 100mg/kg, compound II significantly (P<0.01) reduced gastric injury induced by HCl/ethanol (78%) and indomethacin (88%) better than did reference compound I (48 and 43%, respectively). But the anti-ulcerogenic activity of compound II was completely abolished by the stress-induced ulcer. Reduction of carbonyls with LiAlH(4) (compound III) caused decreased activity, markedly when no protective effect in any of the models was applied (P>0.05). However, compound IV, in which the lactone moiety was changed into an amide, when administered at the same dose (100mg/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.
Melo
Patricia Silva
PS
Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas, cp. 6110, CEP 13081-970, SP, Campinas, Brazil.
Durán
Nelson
N
Hiruma-Lima
Clélia Akiko
CA
Souza-Brito
Alba Regina Monteiro
AR
Haun
Marcela
M
D000818:Animals; D000897:Anti-Ulcer Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D029802:Croton / Q000737:chemistry*; D004224:Diterpenes / Q000302:isolation & purification / Q000627:therapeutic use*; D045785:Diterpenes, Clerodane / Q000737:chemistry / Q000627:therapeutic use; D000431:Ethanol; D006851:Hydrochloric Acid; D007035:Hypothermia; D007213:Indomethacin; D007783:Lactones / Q000302:isolation & purification / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008517:Phytotherapy; D024301:Plant Bark / Q000737:chemistry; D028321:Plant Preparations / Q000627:therapeutic use*; D013315:Stress, Psychological / Q000150:complications; D013329:Structure-Activity Relationship; D014456:Ulcer / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D045785:Diterpenes, Clerodane; D007783:Lactones; D028321:Plant Preparations; C103060:dehydrocrotonin; D000431:Ethanol; D006851:Hydrochloric Acid; D007213:Indomethacin