title: Palau'amine and related oroidin alkaloids dibromophakellin and dibromophakellstatin inhibit the human 20S proteasome.
abstract: We report herein that the oroidin-derived alkaloids palau'amine (1), dibromophakellin (2), and dibromophakellstatin (3) inhibit the proteolytic activity of the human 20S proteasome as well as the (i)20S immunoproteasome catalytic core. Palau'amine is found to prevent the degradation of ubiquitinylated proteins, including IκBα, in cell culture, which may be indicative of the potential mechanism by which these agents exhibit their exciting cytotoxic and immunosuppressive properties.
authors.affiliation: Department of Chemistry, Michigan State University , East Lansing, Michigan 48823, USA.
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Lansdell
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Hewlett
authors.forename: Amanda P
authors.initials: AP
authors.lastname: Skoumbourdis
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Fodor
authors.forename: Ian B
authors.initials: IB
authors.lastname: Seiple
authors.forename: Shun
authors.initials: S
authors.lastname: Su
authors.forename: Phil S
authors.initials: PS
authors.lastname: Baran
authors.forename: Ken S
authors.initials: KS
authors.lastname: Feldman
authors.forename: Jetze J
authors.initials: JJ
authors.lastname: Tepe
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D006146:Guanidines / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry; D061988:Proteasome Inhibitors; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D006146:Guanidines; D006576:Heterocyclic Compounds, 4 or More Rings; D007093:Imidazoles; D016328:NF-kappa B; D061988:Proteasome Inhibitors; D011758:Pyrroles; D013141:Spiro Compounds; C541047:dibromophakellin; C104805:dibromophakellstatin; C438976:palau'amine; D046988:Proteasome Endopeptidase Complex; C077209:oroidin