title: 11-Phenylundeca-5Z,9Z-dienoic Acid: Stereoselective Synthesis and Dual Topoisomerase I/IIα Inhibition.
abstract: (5Z,9Z)-11-Phenylundeca-5,9-dienoic acid was stereoselectively synthesized, based on original cross-cyclomagnesiation of 2-(hepta-5,6-dien-1-yloxy)tetrahydro-2H-pyran and buta-2,3-dien-1-ylbenzene with EtMgBr in the presence of the Cp2TiCl2 catalyst giving 2,5-dialkylydenemagnesacyclopentane in 86% yield. The acid hydrolysis of the product and Jones oxidation of the resulting 2-{[(5Z,9Z)-11-phenylundeca-5,9-dien-1-yl]oxy}tetrahydro-2Н-pyran afforded (5Z,9Z)-11-phenylundeca-5,9-dienoic acid in an overall yield of 75%. A high inhibitory activity of the synthesized acid with respect to human topoisomerase I (hTop1) and II (hTop2α) was detected. Resorting to the data of molecular docking, a mechanism of inhibition was proposed.
authors.affiliation: Institute of Petrochemistry and Catalysis, Russian Academy of Science, Ufa, Russian Federation. DyakonovVA@gmail.com.
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: D'yakonov
authors.forename: Lilya U
authors.initials: LU
authors.lastname: Dzhemileva
authors.forename: Aleksey A
authors.initials: AA
authors.lastname: Makarov
authors.forename: Alfiya R
authors.initials: AR
authors.lastname: Mulyukova
authors.forename: Dmitry S
authors.initials: DS
authors.lastname: Baevd
authors.forename: Elza K
authors.initials: EK
authors.lastname: Khusnutdinova
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Tolstikova
authors.forename: Usein M
authors.initials: UM
authors.lastname: Dzhemilev
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C000604944:11-phenylundeca-5,9-dienoic acid; D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D005231:Fatty Acids, Unsaturated; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D004250:DNA Topoisomerases, Type II