Abstract
Nonthmicin (1), a new polyether polyketide bearing a chlorinated tetronic acid, was isolated from the culture extract of a soil-derived Actinomadura strain. The structure of 1 was elucidated by interpretation of NMR and MS spectroscopic data, and the absolute configuration of 1 was proposed on the basis of the crystal structure of its dechloro congener ecteinamycin (2) also isolated from the same strain. Tetronic acids modified by halogenation have never been reported from natural products. Compounds 1 and 2 were found to have neuroprotective activity and antimetastatic properties at submicromolar concentrations in addition to antibacterial activity.
MeSH terms
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Actinomycetales / chemistry*
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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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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / isolation & purification
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Antineoplastic Agents / pharmacology
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Autophagy
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Cell Survival / drug effects
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Ethers / chemistry
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Furans / chemistry
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Gram-Positive Bacteria / drug effects
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Humans
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Models, Molecular
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Molecular Conformation
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Neoplasm Invasiveness
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Neuroprotective Agents / chemistry*
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Neuroprotective Agents / isolation & purification
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Neuroprotective Agents / pharmacology
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PC12 Cells
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Polyketides / chemistry*
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Polyketides / isolation & purification
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Polyketides / pharmacology
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Rats
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Stereoisomerism
Substances
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Anti-Bacterial Agents
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Antineoplastic Agents
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Ethers
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Furans
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Neuroprotective Agents
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Polyketides
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tetronic acid