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3-Oxabicyclo[3.3.1]nonenes: synthesis and investigation as tyrosyl-DNA phosphodiesterase 1 inhibitors

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Abstract

Compounds with a 3-oxabicyclo[3.3.1]nonane core were prepared from limonene and aromatic aldehydes containing methoxy groups and phthalaldehydes in the presence of montmorillonite K10 and were converted to aromatic amines containing this heterocycle. Some of the products were found to exhibit inhibitory activity in the reaction catalyzed by human tyrosyl-DNA phosphodiesterase 1 in the micromolar range. Bromo derivatives of amines, compounds 6b and 7b, which combine high inhibitory activity and low cytotoxicity, are promising for further studies in order to create new agents for the use in combined anticancer therapy.

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Acknowledgements

The authors are grateful to the Chemical Research Center for Collective Use of the Siberian Branch, Russian Academy of Sciences, for performing spectral and analytical measurements.

Funding

This study was financially supported by the Russian Science Foundation (Project No. 19-13-00040); purification of the TDP1 and TDP2 proteins was performed as a part of project of the Russian Science Foundation (Project No. 21-14-00105) and within the State Assignment for the Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences (No. 121031300041-4).

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Authors and Affiliations

  1. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 9 prosp. Akad. Lavrentieva, 630090, Novosibirsk, Russian Federation

    N. S. Dyrkheeva & O. I. Lavrik

  2. N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 prosp. Akad. Lavrentieva, 630090, Novosibirsk, Russian Federation

    I. V. Ilyina, K. P. Volcho & N. F. Salakhutdinov

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  1. N. S. Dyrkheeva
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  2. I. V. Ilyina
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  4. N. F. Salakhutdinov
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Corresponding author

Correspondence to N. S. Dyrkheeva.

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No human or animal subjects were used in this research.

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Dedicated to the memory of Academician of the Russian Academy of Sciences G. A. Tolstikov (1933–2013).

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, Vol. 72, No. 10, pp. 2525–2535, October, 2023.

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Dyrkheeva, N.S., Ilyina, I.V., Volcho, K.P. et al. 3-Oxabicyclo[3.3.1]nonenes: synthesis and investigation as tyrosyl-DNA phosphodiesterase 1 inhibitors. Russ Chem Bull 72, 2525–2535 (2023). https://doi.org/10.1007/s11172-023-4055-z

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