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New acetylenic derivatives of bile acids as versatile precursors for the preparation of prodrugs. Synthesis and cytotoxicity study

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Abstract

Three groups of bile acid derivatives with acetylenic moieties, such as propargyl, hex-5-ynoyl, and 4,7,10,13-tetraoxahexadec-15-ynoyl ones, were obtained. The cytotoxic activity of the synthesized compounds against hepatocellular carcinoma (HepG2, Huh7), prostate cancer (PC3), and human embryonic kidney (HEK293) cell lines was studied. The parameters enabling estimation of the total lipophilicity of the synthesized bile acid derivatives (logP, TPSA) were calculated. The correlation between the cytotoxic activity and hydrophilic-lipophilic balance of the synthesized compounds was determined. A physicochemical mechanism for the cytotoxic action of bile acid derivatives is proposed.

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Authors and Affiliations

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

    Yu. R. Pavley, E. Yu. Yamansarov, S. A. Evteev, E. V. Lopatukhina, N. V. Zyk, A. S. Erofeev, P. V. Gorelkin & E. K. Beloglazkina

  2. National University of Science and Technology MISIS, 4 Leninskii prosp., 119049, Moscow, Russian Federation

    E. Yu. Yamansarov, E. V. Lopatukhina, A. S. Erofeev & P. V. Gorelkin

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  1. Yu. R. Pavley
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  2. E. Yu. Yamansarov
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  3. S. A. Evteev
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  4. E. V. Lopatukhina
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  5. N. V. Zyk
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  8. E. K. Beloglazkina
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Correspondence to Yu. R. Pavley.

Additional information

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

Compounds were synthesized under the financial support from the Council for Grants at the President of the Russian Federation (grant MK-1450.2021.1.3). The works on cytotoxicity studies were financially supported by the Russian Science Foundation (project No. 20-14-00312).

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. 3, pp. 724–739, March, 2023.

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Pavley, Y.R., Yamansarov, E.Y., Evteev, S.A. et al. New acetylenic derivatives of bile acids as versatile precursors for the preparation of prodrugs. Synthesis and cytotoxicity study. Russ Chem Bull 72, 724–739 (2023). https://doi.org/10.1007/s11172-023-3837-1

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  • DOI: https://doi.org/10.1007/s11172-023-3837-1

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