title: Synthesis of sesquiterpene-inspired derivatives designed for covalent binding and their inhibition of the NF-κB pathway.
abstract: A significant portion of bioactive secondary metabolites are endowed with reactive functionalities that can engage in covalent interactions with their target. Sesquiterpene lactones in particular are rich in Michael acceptors that react with cysteines. Several polycyclic scaffolds derived from total synthesis or readily available polycyclic terpenes were used as the starting point in the synthesis of a library aiming to project mildly reactive functionalities (Michael acceptors or chloroacetates) with diverse geometries. Screening of the library for inhibition of the NF-κB pathway revealed several potent inhibitors that are chemically readily accessible.
authors.affiliation: Institut de Science et d'Ingénierie Supramoléculaires, Université de Strasbourg, CNRS, 8 allée Gaspard Monge, 67000 Strasbourg, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Duplan
authors.forename: Christelle
authors.initials: C
authors.lastname: Serba
authors.forename: Jose
authors.initials: J
authors.lastname: Garcia
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Valot
authors.forename: Sofia
authors.initials: S
authors.lastname: Barluenga
authors.forename: Mélanie
authors.initials: M
authors.lastname: Hoerlé
authors.forename: Muriel
authors.initials: M
authors.lastname: Cuendet
authors.forename: Nicolas
authors.initials: N
authors.lastname: Winssinger
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D008968:Molecular Conformation; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D016328:NF-kappa B; D012717:Sesquiterpenes; D054852:Small Molecule Libraries