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Synthesis and biological evaluation of colchicine and thiocolchicine derivatives bearing a Michael acceptor moiety in ring A

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Abstract

A series of colchicine and thiocolchicine derivatives bearing a Michael acceptor moiety in ring A were synthesized. Some of these compounds exhibit cytotoxic activity in the nanomolar range, efficiently disrupt the mitotic spindle, and cause the accumulation of G2/M-phase cells resulting in the development of apoptosis. These derivatives can be covalently bound to the cysteine residues at the colchicine-binding site of tubulin.

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Authors and Affiliations

  1. N. I. Lobachevsky Nizhny Novgorod State University, 23 prosp. Gagarina, 603950, Nizhny Novgorod, Russian Federation

    E. A. Mol’kova, E. S. Shchegravina, V. F. Otvagin, N. S. Kuzmina, Yu. B. Malysheva, E. A. Zaburdaeva & A. Yu. Fedorov

  2. Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 ul. Miklukho-Maklaya, 117997, Moscow, Russian Federation

    E. V. Svirshchevskaya

Authors
  1. E. A. Mol’kova
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  2. E. S. Shchegravina
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  3. V. F. Otvagin
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  4. N. S. Kuzmina
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  5. Yu. B. Malysheva
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  6. E. V. Svirshchevskaya
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  7. E. A. Zaburdaeva
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  8. A. Yu. Fedorov
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Corresponding author

Correspondence to A. Yu. Fedorov.

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The authors declare no competing interests.

Additional information

This study was financially supported by the Russian Science Foundation (Project No. 19-13-00158).

No human or animal subjects were used in this research.

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 564–571, March, 2022.

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Mol’kova, E.A., Shchegravina, E.S., Otvagin, V.F. et al. Synthesis and biological evaluation of colchicine and thiocolchicine derivatives bearing a Michael acceptor moiety in ring A. Russ Chem Bull 71, 564–571 (2022). https://doi.org/10.1007/s11172-022-3449-7

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  • DOI: https://doi.org/10.1007/s11172-022-3449-7

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