11-Phenylundeca-5Z,9Z-dienoic Acid: Stereoselective Synthesis and Dual Topoisomerase I/II alpha Inhibition

11-Phenylundeca-5Z,9Z-dienoic Acid: Stereoselective Synthesis and Dual Topoisomerase I/II alpha Inhibition Full article

Journal

Current Cancer Drug Targets
ISSN: 1568-0096 , E-ISSN: 1873-5576

Output data

Year: 2015, Volume: 15, Number: 6, Pages: 504-510 Pages count : DOI: 10.2174/1568009615666150506093155

Tags

Cyclomagnesiation; docking; fatty acids; homogeneous catalysis; novel topoisomerase I and II alpha inhibitors; stereoselective synthesis of 5Z,9Z-dienoic acid

Authors

D'yakonov Vladimir A. ¹ , Dzhemileva Lilya U. ^2,3 , Makarov Aleksey A. ¹ , Mulyukova Alfiya R. ¹ , Baev Dmitry S. ⁴ , Khusnutdinova Elza K. ² , Tolstikova Tatiana G. ⁴ , Dzhemilev Usein M. ¹

Affiliations

1	(Данные Web of science) Russian Acad Sci, Inst Petrochem & Catalysis, Ufa 450001, Russia
2	(Данные Web of science) Bashkir State Univ, Dept Genet & Fundamental Med, Ufa 450074, Bashkortostan, Russia
3	(Данные Web of science) Bashkir State Med Univ, Dept Immunol & Human Reprod Hlth, Ufa, Bashkortostan, Russia
4	(Данные Web of science) Russian Acad Sci, Siberian Branch, NN Vorozhtsov Novosibirsk Inst Organ Chem, Novosibirsk, Russia

(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-2H-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 (hTop2 alpha) was detected. Resorting to the data of molecular docking, a mechanism of inhibition was proposed.

D'yakonov V.A. , Dzhemileva L.U. , Makarov A.A. , Mulyukova A.R. , Baev D.S. , Khusnutdinova E.K. , Tolstikova T.G. , Dzhemilev U.M.
11-Phenylundeca-5Z,9Z-dienoic Acid: Stereoselective Synthesis and Dual Topoisomerase I/II alpha Inhibition
Current Cancer Drug Targets. 2015. V.15. N6. P.504-510. DOI: 10.2174/1568009615666150506093155 WOS Scopus РИНЦ

Published print:

Aug 5, 2015

Web of science	WOS:000359252500007
Scopus	2-s2.0-84939809728
Elibrary	24938562
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