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nZ,(n + 4)Z-Dienoic fatty acids: a new method for the synthesis and inhibitory action on topoisomerase I and IIα

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Abstract

An original, effective approach to the stereoselective method for the synthesis of higher unsaturated acids containing a 1Z,5Z-diene group in 61–75 % yields and with >98 % selectivity based on the new intermolecular Cp2TiCl2-catalyzed cross-cyclomagnesiation of terminal aliphatic and O-containing 1,2-diene with Grignard reagents has been developed. The inhibitory action of the obtained dienoic acids on the human topoisomerase I and II was studied. Resorting to the data of molecular docking, a probable mechanism of inhibition was proposed.

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Acknowledgments

This work was performed under financial support from the Russian Science Foundation (Grant 14-13-00263).

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Authors and Affiliations

  1. Institute of Petrochemistry and Catalysis of Russian Academy of Sciences, 141 Prospekt Oktyabrya, Ufa, Bashkortostan, Russian Federation, 450075

    Vladimir A. D’yakonov, Aleksey A. Makarov, Alfiya R. Mulyukova & Usein M. Dzhemilev

  2. Department of Immunology and Human’s Reproductive Health, Bashkir State Medical University, 3 Lenin Street, Ufa, Bashkortostan, Russian Federation, 450003

    Lilya U. Dzhemileva

  3. N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, Novosibirsk, Russian Federation, 630090

    Dmitry S. Baev & Tatiana G. Tolstikova

  4. Department of Genetics and Fundamental Medicine, Bashkir State University, 32 Zaki Validi Street, Ufa, Bashkortostan, Russian Federation, 450043

    Elza K. Khusnutdinova

Authors
  1. Vladimir A. D’yakonov
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  2. Lilya U. Dzhemileva
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  3. Aleksey A. Makarov
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  4. Alfiya R. Mulyukova
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  5. Dmitry S. Baev
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  6. Elza K. Khusnutdinova
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  7. Tatiana G. Tolstikova
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  8. Usein M. Dzhemilev
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Corresponding authors

Correspondence to Vladimir A. D’yakonov or Lilya U. Dzhemileva.

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44_2015_1446_MOESM1_ESM.docx

Text giving experimental details, characterization data of acids, copies of NMR spectra. This material is available free of charge via the Internet. (DOCX 766 kb)

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D’yakonov, V.A., Dzhemileva, L.U., Makarov, A.A. et al. nZ,(n + 4)Z-Dienoic fatty acids: a new method for the synthesis and inhibitory action on topoisomerase I and IIα. Med Chem Res 25, 30–39 (2016). https://doi.org/10.1007/s00044-015-1446-1

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  • DOI: https://doi.org/10.1007/s00044-015-1446-1

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