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New podophyllotoxin and epipodophyllotoxin derivatives with substituted isoxazole fragments

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Abstract

A series of podophyllotoxin and epipodophyllotoxin esters with methylisoxazole fragments containing a halogen atom or a nitro group at position 4 of the heterocycle was synthesized. The starting isoxazolecarboxylic acids were obtained by bromination, iodination, or nitration of 5-methylisoxazole-3-carboxylic acid, which then were converted to the target esters by esterification in the DCC/DMAP or EDC/DMAP system. The results of molecular docking of podophyllotoxin and epipodophyllotoxin esters with the iodine-containing isoxazole derivatives predicted their ability to bind to tubulin and topoisomerase II, respectively, and do not exclude the possibility of the formation of halogen bonds with target proteins. The primary bioscreening showed that all compounds obtained at a concentration of 100 nmol L−1 caused a decrease in the number of A549 and VA13 cells by 40–60% after 72 h of treatment.

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Authors and Affiliations

  1. Department of Chemistry, Lomonosov Moscow State University, Build. 3, 1 Leninskie Gory, 119991, Moscow, Russian Federation

    N. A. Zefirov, E. V. Nurieva, A. V. Mamaeva, D. A. Vasilenko, K. S. Sadovnikov, E. B. Averina, A. Yu. Kolchanova, E. R. Milaeva & O. N. Zefirova

Authors
  1. N. A. Zefirov
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  2. E. V. Nurieva
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  3. A. V. Mamaeva
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  4. D. A. Vasilenko
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  5. K. S. Sadovnikov
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  6. E. B. Averina
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  7. A. Yu. Kolchanova
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  8. E. R. Milaeva
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  9. O. N. Zefirova
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Correspondence to E. V. Nurieva.

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Dedicated to Academician of the Russian Academy of Sciences I. P. Beletskaya on the occasion of her anniversary.

This work was financially supported by the Russian Science Foundation (Project No. 22-63-00016).

No human or animal subjects were used in this research.

The authors declare no competing interests.

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, Vol. 72, No. 4, pp. 1029–1035, April, 2023.

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Zefirov, N.A., Nurieva, E.V., Mamaeva, A.V. et al. New podophyllotoxin and epipodophyllotoxin derivatives with substituted isoxazole fragments. Russ Chem Bull 72, 1029–1035 (2023). https://doi.org/10.1007/s11172-023-3868-5

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  • DOI: https://doi.org/10.1007/s11172-023-3868-5

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