Stereoselective synthesis of 11-phenylundeca-5Z,9Z-dienoic acid and investigation of its human topoisomerase I and IIα inhibitory activity.
(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 Cp2TiCl2 catalyst giving 2,5-dialkylidenemagnesacyclopentane in 86% yield. The acid hydrolysis of the product and the 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 determined.
Institute of Petrochemistry and Catalysis, Russian Academy of Science, 141 Prospekt Oktyabrya, 450075, Ufa, Russian Federation. Electronic address: DyakonovVA@gmail.com.
Vladimir A
VA
D'yakonov
Department of Genetics and Fundamental Medicine, Bashkir State University, 32 Zaki Validi Street, Ufa, Bashkortostan 450043, Russian Federation; Department of Immunology and Human Reproductive Health, Bashkir State Medical University, 3 Lenin Street, Ufa, Bashkortostan 450003, Russian Federation. Electronic address: Dzhemilev@mail.ru.
Lilya U
LU
Dzhemileva
Institute of Petrochemistry and Catalysis, Russian Academy of Science, 141 Prospekt Oktyabrya, 450075, Ufa, Russian Federation.
Aleksey A
AA
Makarov
Institute of Petrochemistry and Catalysis, Russian Academy of Science, 141 Prospekt Oktyabrya, 450075, Ufa, Russian Federation.
Alfiya R
AR
Mulukova
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, Novosibirsk 630090, Russian Federation.
Dmitry S
DS
Baev
Department of Genetics and Fundamental Medicine, Bashkir State University, 32 Zaki Validi Street, Ufa, Bashkortostan 450043, Russian Federation.
Elza K
EK
Khusnutdinova
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, Novosibirsk 630090, Russian Federation. Electronic address: ttg@front.ru.
Tatiana G
TG
Tolstikova
Institute of Petrochemistry and Catalysis, Russian Academy of Science, 141 Prospekt Oktyabrya, 450075, Ufa, Russian Federation.
Usein M
UM
Dzhemilev
D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D003198:Computer Simulation; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
C000604944:11-phenylundeca-5,9-dienoic acid; D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D005231:Fatty Acids, Unsaturated; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D004250:DNA Topoisomerases, Type II
5Z,9Z-Dienoic acids; DNA-binding; Molecular docking; Topoisomerase I; Topoisomerase IIα