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New C(4)-esters of podophyllotoxin and epipodophyllotoxin with heterocyclic moieties

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Abstract

Esters of podophyllotoxin and epipodophyllotoxin with 4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)butanoic and (4R)-N-(tert-butoxycarbonyl)-1,3-thiazolidine-4-carboxylic acids were synthesized. The obtained esters are less lipophilic analogs of the known podophyllotoxin esters. Two new compounds were found to demonstrate selective cytotoxicity against cancer cells in the mixed culture of lung carcinoma cells (A549) and noncancerous lung fibroblasts (VA13). Podophyllotoxin ester with (4R)-1,3-thiazolidine-4-carboxylic acid moiety was also synthesized. This compound like its pyrrolidine analog was found to be nonselective but in contrast two orders of magnitude less active. Selectivity against cancer cells in combination with acceptable lipophilicity of the podophyllotoxin and epipodophyllotoxin esters bearing the tert-butoxycarbonylthiazolidine moiety makes these compounds promising for further in vitro and in vivo evaluation.

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Authors and Affiliations

  1. Lomonosov Moscow State University, 1 Leninskie Gory, 119991, Moscow, Russian Federation

    I. A. Elisseev, E. V. Nurieva, N. A. Zefirov, A. Yu. Kolchanova, D. A. Skvortsov, E. R. Milaeva & O. N. Zefirova

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  1. I. A. Elisseev
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  2. E. V. Nurieva
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  3. N. A. Zefirov
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  4. A. Yu. Kolchanova
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  5. D. A. Skvortsov
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  6. E. R. Milaeva
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  7. O. N. Zefirova
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Corresponding author

Correspondence to E. V. Nurieva.

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Additional information

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.

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, Vol. 72, No. 9, pp. 2191–2196, September, 2023.

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Elisseev, I.A., Nurieva, E.V., Zefirov, N.A. et al. New C(4)-esters of podophyllotoxin and epipodophyllotoxin with heterocyclic moieties. Russ Chem Bull 72, 2191–2196 (2023). https://doi.org/10.1007/s11172-023-4015-7

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  • DOI: https://doi.org/10.1007/s11172-023-4015-7

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