Abstract
In addition to the sesquiterpene-phenol aureols (1), 6'-chloroaureol (2), and aureol acetate (3), eight indole alkaloids including the new N-3'-ethylaplysinopsin (9) have been isolated from the Jamaican sponge Smenospongia aurea. Makaluvamine O (10), a new member of the pyrroloiminoquinone class, was also isolated. The structures were characterized by spectroscopic methods, and two new derivatives of aureol were prepared to optimize the biological activity. Aureol N,N-dimethyl thiocarbamate (1a) and 6-bromoaplysinopsin (7) exhibit significant antimalarial and antimycobacterial activity in vitro. Compound 6 showed activity against the Plasmodium enzyme plasmepsin II. The 6-bromo-2'-de-N-methylaplysinopsin (6), 6-bromoaplysinopsin (7), and N-3'-ethylaplysinopsin (9) displaced high-affinity [(3)H]antagonist ligands from cloned human serotonin 5-HT(2) receptor subtypes, whereas the other compounds tested did not. Remarkably, the 6-bromo-2'-de-N-methylaplysinopsin (6) showed a > 40-fold selectivity for the 5-HT(2C) subtype over the 5-HT(2A) subtype.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Anti-Infective Agents / chemistry
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Anti-Infective Agents / isolation & purification*
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Anti-Infective Agents / pharmacology
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Antimalarials / chemistry
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Antimalarials / isolation & purification*
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Antimalarials / pharmacology
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Aspartic Acid Endopeptidases / metabolism
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Cell Membrane / drug effects
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Cells, Cultured / drug effects
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Chlorocebus aethiops
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Humans
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Indole Alkaloids / chemistry
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Indole Alkaloids / isolation & purification
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Indole Alkaloids / pharmacology
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Jamaica
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Molecular Conformation
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Molecular Structure
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Nuclear Magnetic Resonance, Biomolecular
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Porifera / chemistry*
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Protozoan Proteins
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Pyrroles / chemistry
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Pyrroles / isolation & purification
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Pyrroles / pharmacology
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Quinones / chemistry
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Quinones / isolation & purification
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Quinones / pharmacology
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Receptors, Serotonin / drug effects*
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Sesquiterpenes / chemistry
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Sesquiterpenes / isolation & purification*
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Sesquiterpenes / pharmacology
Substances
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6'-chloroaureol
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6-bromo-2'-de-N-methylaplysinopsin
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Anti-Infective Agents
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Antimalarials
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Indole Alkaloids
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N-3'-ethylaplysinopsin
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Protozoan Proteins
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Pyrroles
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Quinones
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Receptors, Serotonin
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Sesquiterpenes
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aureol
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aureol acetate
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makaluvamine O
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Aspartic Acid Endopeptidases
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plasmepsin II