Structure activity relationship in the cytoprotective effect of helenalin and related compounds

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

Drug Design and Discovery

Harwood Academic Publishers GmbH

Año: 1994 vol. 11 p. 23 - 28

1055-9612

Our previous reports indica te that the cytoprotective effect of helenalin and several sesquiterpene lactonesis mediated through a Michael reaction between the sulfhydryl containing peptides of the gastric mucosaand Michael acceptors present in the sesquiterpene lactone molecules.In the present work the different altemative active sites in molecules containing up to three places whichcould actas viable Michael acceptors are evaluated. To do this, an extensive conformational and electronicstudy of helenalin and its derivatives was carried out.The experimental and theoretical results obtained show the y-lactone and cyclopentenone groups to bethe biologically active places of the molecules under study, whereas tiglic and angelic substituents in thesecompounds show different behavior as Michael acceptors.