Structure activity relationship in the gastric cytoprotective effect of several sesquiterpene lactones

O.GIORDANO; M.PESTCHANKER; E.GUERREIRO; J.SAAD; ENRIZ R.D.; A.M RODRIGUEZ; E.A.JAUREGUI

JOURNAL OF MEDICINAL CHEMISTRY

AMER CHEMICAL SOC

Lugar: Washington; Año: 1992 vol. 32 p. 2452 - 2458

0022-2623

The structural requirements for the gastric cytoprotective activity of several sesquiterpene lactones are reported. A theoretical-xperimental 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 muma and Michael amptors 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.