Short Route to the Total Synthesis of Natural Muricadienin and Investigation of Its Cytotoxic Properties.

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).

• Authors: Usein M Dzhemilev, Vladimir A D'yakonov, Regina A Tuktarova, Lilya U Dzhemileva, Svetlana R Ishmukhametova, Milyausha M Yunusbaeva, Armin de Meijere
• Journal: Journal of natural products (J Nat Prod) Vol. 79 Issue 8 Pg. 2039-44 (08 26 2016) ISSN: 1520-6025 [Electronic] United States
• PMID: 27533261 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetogenins
• Antineoplastic Agents
• Topoisomerase I Inhibitors
• muricadienin
• Benzethonium
• DNA Topoisomerases, Type I
• TOP1 protein, human
• DNA Topoisomerases, Type II

Topics

• Acetogenins (chemical synthesis, chemistry, pharmacology)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Benzethonium (chemistry)
• DNA Topoisomerases, Type I (metabolism)
• DNA Topoisomerases, Type II (metabolism)
• Drug Screening Assays, Antitumor
• HEK293 Cells
• Humans
• Molecular Structure
• Topoisomerase I Inhibitors (pharmacology)