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

(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%...

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Bibliographic Details
Published in:	Current cancer drug targets Vol. 15; no. 6; p. 504
Main Authors:	D'yakonov, Vladimir A, Dzhemileva, Lilya U, Makarov, Aleksey A, Mulyukova, Alfiya R, Baevd, Dmitry S, Khusnutdinova, Elza K, Tolstikova, Tatiana G, Dzhemilev, Usein M
Format:	Journal Article
Language:	English
Published:	Netherlands 01-08-2015
Subjects:	Antigens, Neoplasm - chemistry Antigens, Neoplasm - metabolism Binding Sites Catalytic Domain DNA Topoisomerases, Type I - chemistry DNA Topoisomerases, Type I - metabolism DNA Topoisomerases, Type II - chemistry DNA Topoisomerases, Type II - metabolism DNA-Binding Proteins - antagonists & inhibitors DNA-Binding Proteins - chemistry DNA-Binding Proteins - metabolism Drug Design Fatty Acids, Unsaturated - chemical synthesis Fatty Acids, Unsaturated - metabolism Fatty Acids, Unsaturated - pharmacology Humans Molecular Docking Simulation Protein Binding Protein Conformation Structure-Activity Relationship Topoisomerase I Inhibitors - chemical synthesis Topoisomerase I Inhibitors - metabolism Topoisomerase I Inhibitors - pharmacology Topoisomerase II Inhibitors - chemical synthesis Topoisomerase II Inhibitors - metabolism Topoisomerase II Inhibitors - pharmacology
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Summary:	(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.
ISSN:	1873-5576
DOI:	10.2174/1568009615666150506093155