title: Structure-activity relationship in the gastric cytoprotective effect of several sesquiterpene lactones.
abstract: 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.
authors.affiliation: Departamento de Química Orgánica, Universidad Nacional de San Luis, Chacabuco y Pedernera, San Luis, Argentina.
authors.forename: O S
authors.initials: OS
authors.lastname: Giordano
authors.forename: M J
authors.initials: MJ
authors.lastname: Pestchanker
authors.forename: E
authors.initials: E
authors.lastname: Guerreiro
authors.forename: J R
authors.initials: JR
authors.lastname: Saad
authors.forename: R D
authors.initials: RD
authors.lastname: Enriz
authors.forename: A M
authors.initials: AM
authors.lastname: Rodríguez
authors.forename: E A
authors.initials: EA
authors.lastname: Jáuregui
authors.forename: J
authors.initials: J
authors.lastname: Guzmán
authors.forename: A O
authors.initials: AO
authors.lastname: María
authors.forename: G H
authors.initials: GH
authors.lastname: Wendel
mesh_terms: D007783:Lactones / Q000494:pharmacology*; D008968:Molecular Conformation; D012717:Sesquiterpenes / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D007783:Lactones; D012717:Sesquiterpenes