The synthesis of spermine analogs of the shark aminosterol squalamine.
Aminosterols isolated from the dogfish shark Squalus acanthias are promising therapeutic agents in the treatment of infection and cancer. One of these, MSI-1436, has been shown to possess antimicrobial activity slightly better than squalamine. In this study, a series of analogs of MSI-1436 have been synthesized from stigmasterol. The 7 alpha-hydroxy substituent of MSI-1436 was either omitted or the stereochemistry modified to the 7 beta position. Also, analogs of MSI-1436 with 24-sulfate, 24-amino, and 24-hydroxy substituents were synthesized in order to assess the importance of the side chain functional group on antimicrobial activity. All of the analogs possess significant antimicrobial activity, suggesting that substitution at C7 and C24 of the aminosterols plays a minor role in their antimicrobial potency.
Shu
Youheng
Y
Chemistry Department, Villanova University, Villanova, PA 19085, USA.
Jones
Stephen R
SR
Kinney
William A
WA
Selinsky
Barry S
BS
D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D002776:Cholestanes / Q000737:chemistry* / Q000494:pharmacology; D002777:Cholestanols / Q000737:chemistry* / Q000494:pharmacology; D004284:Dogfish; D004926:Escherichia coli / Q000187:drug effects; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013096:Spermine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D013237:Stereoisomerism; D013265:Stigmasterol / Q000737:chemistry; D013329:Structure-Activity Relationship
C441128:3-N-1(spermine)-7, 24-dihydroxy-5-cholestane 24-sulfate; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D002776:Cholestanes; D002777:Cholestanols; D013096:Spermine; D013265:Stigmasterol; C079655:squalamine