STRUCTURE ACTIVITY RELATIONSHIP IN THE GASTRIC CYTOPROTECTIVE EFFECT OF SEVERAL SESQUITERPENE LACTONES

被引:91
作者
GIORDANO, OS
PESTCHANKER, MJ
GUERREIRO, E
SAAD, JR
ENRIZ, RD
RODRIGUEZ, AM
JAUREGUI, EA
GUZMAN, J
MARIA, AOM
WENDEL, GH
机构
[1] UNIV NACL SAN LUIS,CATEDRA FARMACOL,RA-5700 SAN LUIS,ARGENTINA
[2] UNIV NACL SAN LUIS,DEPT QUIM GEN & INORGAN,RA-5700 SAN LUIS,ARGENTINA
关键词
D O I
10.1021/jm00091a013
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The structural requirements for the gastric cytoprotective activity of several sesquiterpene lactones are reported. A theoretical-experimental study on the potentially active centers is carried out. The biological evaluation of reduced analogues and the simulation of the molecular interactions between these compounds and an endogenous cysteine residue suggest that the presence of a non sterically hindered Michael acceptor seems to be an essential structural requirement for the cytoprotective activity in this family of compounds. This observation suggests that cytoprotection is mediated through a Michael reaction between the sulfhydryl-containing peptides of the mucosa and Michael acceptors present in the molecules under study. This mechanism of action is in addition to and distinct from the one proposed in our previous paper, namely, that these sesquiterpenes stimulate endogenous synthesis of prostaglandins.
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页码:2452 / 2458
页数:7
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