title: 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.affiliation: Laboratory of Catalytic Synthesis, Institute of Petrochemistry and Catalysis of RAS (IPC RAS) , Prospect Octyabrya, 141, 450075, Ufa, Russian Federation.
authors.forename: Usein M
authors.initials: UM
authors.lastname: Dzhemilev
authors.affiliation: Laboratory of Catalytic Synthesis, Institute of Petrochemistry and Catalysis of RAS (IPC RAS) , Prospect Octyabrya, 141, 450075, Ufa, Russian Federation.
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: D'yakonov
authors.affiliation: Laboratory of Catalytic Synthesis, Institute of Petrochemistry and Catalysis of RAS (IPC RAS) , Prospect Octyabrya, 141, 450075, Ufa, Russian Federation.
authors.forename: Regina A
authors.initials: RA
authors.lastname: Tuktarova
authors.affiliation: Laboratory of Catalytic Synthesis, Institute of Petrochemistry and Catalysis of RAS (IPC RAS) , Prospect Octyabrya, 141, 450075, Ufa, Russian Federation.|Department of Immunology and Human Reproductive Health, Bashkir State Medical University , Lenin Street, 3, 450003, Ufa, Russian Federation.|Institute of Biochemistry and Genetics, Ufa Scientific Centre of Russian Academy of Sciences , Prospect Octyabrya, 71, 450054, Ufa, Russian Federation.
authors.forename: Lilya U
authors.initials: LU
authors.lastname: Dzhemileva
authors.affiliation: Laboratory of Catalytic Synthesis, Institute of Petrochemistry and Catalysis of RAS (IPC RAS) , Prospect Octyabrya, 141, 450075, Ufa, Russian Federation.
authors.forename: Svetlana R
authors.initials: SR
authors.lastname: Ishmukhametova
authors.affiliation: Institute of Biochemistry and Genetics, Ufa Scientific Centre of Russian Academy of Sciences , Prospect Octyabrya, 71, 450054, Ufa, Russian Federation.
authors.forename: Milyausha M
authors.initials: MM
authors.lastname: Yunusbaeva
authors.affiliation: Institut für Organische und Biomolekulare Chemie der Georg-August-Universität Göttingen , Tammannstrasse 2, 37077 Göttingen, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: de Meijere
mesh_terms: D054378:Acetogenins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001558:Benzethonium / Q000737:chemistry; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D057809:HEK293 Cells; D006801:Humans; D015394:Molecular Structure; D059004:Topoisomerase I Inhibitors / Q000494:pharmacology
chemical_list: D054378:Acetogenins; D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; C000599601:muricadienin; D001558:Benzethonium; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D004250:DNA Topoisomerases, Type II