title: Aminosterols from the dogfish shark Squalus acanthias.
abstract: Seven new aminosterols related to squalamine (8) were isolated from the liver of the dogfish shark Squalus acanthias. Their structures (1-7) were determined using spectroscopic methods, including 2D NMR and HRFABMS. These aminosterols possess a relatively invariant cholestane skeleton with a trans AB ring junction, a spermidine or spermine attached equatorially at C3, and a steroidal side-chain that may be sulfated. The structure of the lone spermine conjugate, 7 (MSI-1436), was confirmed by its synthesis from (5alpha,7alpha, 24R)-7-hydroxy-3-ketocholestan-24-yl sulfate. Some members of this family of aminosterols exhibit a broad spectrum of antimicrobial activity comparable to squalamine.
authors.affiliation: Magainin Pharmaceuticals, Inc., 5110 Campus Drive, Plymouth Meeting, Pennsylvania 19462, USA.
authors.forename: M N
authors.initials: MN
authors.lastname: Rao
authors.forename: A E
authors.initials: AE
authors.lastname: Shinnar
authors.forename: L A
authors.initials: LA
authors.lastname: Noecker
authors.forename: T L
authors.initials: TL
authors.lastname: Chao
authors.forename: B
authors.initials: B
authors.lastname: Feibush
authors.forename: B
authors.initials: B
authors.lastname: Snyder
authors.forename: I
authors.initials: I
authors.lastname: Sharkansky
authors.forename: A
authors.initials: A
authors.lastname: Sarkahian
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: S R
authors.initials: SR
authors.lastname: Jones
authors.forename: W A
authors.initials: WA
authors.lastname: Kinney
authors.forename: M
authors.initials: M
authors.lastname: Zasloff
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004284:Dogfish / Q000378:metabolism*; D008099:Liver / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013261:Sterols / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D013261:Sterols