Aminosterols from the dogfish shark Squalus acanthias.
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.
Rao
M N
MN
Magainin Pharmaceuticals, Inc., 5110 Campus Drive, Plymouth Meeting, Pennsylvania 19462, USA.
Shinnar
A E
AE
Noecker
L A
LA
Chao
T L
TL
Feibush
B
B
Snyder
B
B
Sharkansky
I
I
Sarkahian
A
A
Zhang
X
X
Jones
S R
SR
Kinney
W A
WA
Zasloff
M
M
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
D000900:Anti-Bacterial Agents; D013261:Sterols