Structure-activity relationship in the cytoprotective effect of helenalin and related compounds.
Our previous reports indicate that the cytoprotective effect of helenalin and several sesquiterpene lactones is mediated through a Michael reaction between the sulfhydryl containing peptides of the gastric mucosa and Michael acceptors present in the sesquiterpene lactone molecules. In the present work the different alternative active sites in molecules containing up to three places which could act as viable Michael acceptors are evaluated. To do this, an extensive conformational and electronic study of helenalin and its derivatives was carried out. The experimental and theoretical results obtained show the gamma-lactone and cyclopentenone groups to be the biologically active places of the molecules under study, whereas tiglic and angelic substituents in these compounds show different behavior as Michael acceptors.
Enriz
R D
RD
Departamento de Química-Física, Universidad Nacional de San Luis, Facultad de Química, Bioquímica y Farmacia, Argentina.
Rodriguez
A M
AM
Jáuregui
E A
EA
Pestchanker
M J
MJ
Giordano
O S
OS
Guzmán
J
J
D002316:Cardiotonic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008968:Molecular Conformation; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045789:Sesquiterpenes, Guaiane; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002316:Cardiotonic Agents; D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; C001329:helenalin