title: Neuroactive diol and acyloin metabolites from cone snail-associated bacteria.
abstract: The bacterium Gordonia sp. 647W.R.1a.05 was cultivated from the venom duct of the cone snail, Conus circumcisus. The Gordonia sp. organic extract modulated the action potential of mouse dorsal root ganglion neurons. Assay-guided fractionation led to the identification of the new compound circumcin A (1) and 11 known analogs (2-12). Two of these compounds, kurasoin B (7) and soraphinol A (8), were active in a human norepinephrine transporter assay with Ki values of 2575 and 867 nM, respectively. No neuroactivity had previously been reported for compounds in this structural class. Gordonia species have been reproducibly isolated from four different cone snail species, indicating a consistent association between these organisms.
authors.affiliation: Department of Medicinal Chemistry, L.S. Skaggs Pharmacy Institute, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Zhenjian
authors.initials: Z
authors.lastname: Lin
authors.forename: Lenny
authors.initials: L
authors.lastname: Marett
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Hughen
authors.forename: Malem
authors.initials: M
authors.lastname: Flores
authors.forename: Imelda
authors.initials: I
authors.lastname: Forteza
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Ammon
authors.forename: Gisela P
authors.initials: GP
authors.lastname: Concepcion
authors.forename: Samuel
authors.initials: S
authors.lastname: Espino
authors.forename: Baldomero M
authors.initials: BM
authors.lastname: Olivera
authors.forename: Gary
authors.initials: G
authors.lastname: Rosenberg
authors.forename: Margo G
authors.initials: MG
authors.lastname: Haygood
authors.forename: Alan R
authors.initials: AR
authors.lastname: Light
authors.forename: Eric W
authors.initials: EW
authors.lastname: Schmidt
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D052078:Conus Snail / Q000382:microbiology*; D005233:Fatty Alcohols / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology; D033601:Gordonia Bacterium / Q000502:physiology*; D006801:Humans; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D013559:Symbiosis
chemical_list: D001688:Biological Products; D005233:Fatty Alcohols; D050484:Norepinephrine Plasma Membrane Transport Proteins; C011159:acyloin
keywords: Natural product; Neuroassay; Symbiont