Abstract
Cytotoxicity-guided fractionation of a Guamanian cyanobacterial collection yielded the new compounds amantelides A (1) and B (2). These polyketides are characterized by a 40-membered macrolactone ring consisting of a 1,3-diol and contiguous 1,5-diol units and a tert-butyl substituent. Amantelide A (1) displayed potent cytotoxicity with submicromolar IC₅₀ against HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cell lines. Acetylation of the hydroxy group at C-33 in 2 caused a close to 10-fold decrease in potency. Exhaustive acetylation of the hydroxy groups abrogated the antiproliferative activity of amantelide A (1) by 20-67-fold. Further bioactivity assessment of 1 against bacterial pathogens and marine fungi indicated a broad spectrum of bioactivity.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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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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Antifungal Agents / chemistry
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Antifungal Agents / isolation & purification*
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Antifungal Agents / pharmacology*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / isolation & purification*
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Antineoplastic Agents / pharmacology*
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Cyanobacteria / chemistry*
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Drug Screening Assays, Antitumor
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HT29 Cells
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HeLa Cells
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Humans
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Inhibitory Concentration 50
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Macrolides / chemistry
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Macrolides / isolation & purification*
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Macrolides / pharmacology*
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Marine Biology
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Microbial Sensitivity Tests
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Molecular Structure
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Protein Synthesis Inhibitors
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Anti-Bacterial Agents
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Antifungal Agents
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Antineoplastic Agents
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Macrolides
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Protein Synthesis Inhibitors
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amantelide A
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amantelide B