Abstract
In the course of our studies on anti-mycobacterial substances from marine organisms, the known dimeric sphingolipid, leucettamol A (1), was isolated as an active component, together with the new bromopyrrole alkaloid, 5-bromophakelline (2), and twelve known congeners from the Indonesian marine sponge Agelas sp. The structure of 2 was elucidated based on its spectroscopic data. Compound 1 and its bis TFA salt showed inhibition zones of 12 and 7 mm against Mycobacterium smegmatis at 50 μg/disk, respectively, while the N,N'-diacetyl derivative (1a) was not active at 50 μg/disk. Therefore, free amino groups are important for anti-mycobacterial activity. This is the first study to show the anti-mycobacterial activity of a bisfunctionalized sphingolipid. Compound 13 exhibited weak PTP1B inhibitory activity (29% inhibition at 35 μM).
Keywords:
Bromopyrrole alkaloid; Leucettamol A; Marine sponge Agelas sp.; Mycobacterium smegmatis; Protein tyrosine phosphatase 1B.
MeSH terms
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Agelas / chemistry*
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Alkaloids / chemistry
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Alkaloids / isolation & purification
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Alkaloids / pharmacology
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Animals
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / isolation & purification
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Anti-Bacterial Agents / pharmacology*
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Biological Products / chemistry
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Biological Products / pharmacology
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / isolation & purification
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Enzyme Inhibitors / pharmacology
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Indonesia
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Molecular Structure
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Mycobacterium smegmatis / drug effects*
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Mycobacterium smegmatis / growth & development
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Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors
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Pyrroles / chemistry
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Pyrroles / isolation & purification*
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Pyrroles / pharmacology
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Sphingolipids / chemistry
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Sphingolipids / isolation & purification
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Sphingolipids / pharmacology*
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Structure-Activity Relationship
Substances
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5-bromophakelline
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Alkaloids
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Anti-Bacterial Agents
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Biological Products
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Enzyme Inhibitors
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Pyrroles
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Sphingolipids
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leucettamol A
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Protein Tyrosine Phosphatase, Non-Receptor Type 1