Abstract
An original synthesis of the acetogenin muricadienin, the bioprecursor of solamin, has been developed. The key step in the five-step 41% overall yield synthesis is the catalytic cross-cyclomagnesiation reaction of functionally substituted 1,2-dienes with EtMgBr in the presence of Cp2TiCl2 and magnesium metal. It has been demonstrated for the first time that muricadienin exhibits a moderate in vitro inhibitory activity against topoisomerases I and IIα, key cell cycle enzymes. Using flow cytometry, muricadienin was shown to have high cytotoxicity toward the HEK293 kidney cancer cells (IC50 0.39 μM).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetogenins* / chemical synthesis
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Acetogenins* / chemistry
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Acetogenins* / pharmacology
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Antineoplastic Agents* / chemical synthesis
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Antineoplastic Agents* / chemistry
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Antineoplastic Agents* / pharmacology
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Benzethonium / chemistry
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DNA Topoisomerases, Type I / metabolism
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DNA Topoisomerases, Type II / metabolism
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Drug Screening Assays, Antitumor
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HEK293 Cells
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Humans
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Molecular Structure
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Topoisomerase I Inhibitors / pharmacology
Substances
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Acetogenins
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Antineoplastic Agents
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Topoisomerase I Inhibitors
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muricadienin
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Benzethonium
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DNA Topoisomerases, Type I
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TOP1 protein, human
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DNA Topoisomerases, Type II