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Synthesis and cytotoxic activity of 3-amino substituted fusidane triterpenoids

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Abstract

New 3-amino substituted derivatives, containing linear, aromatic, and heterocyclic fragments, as well as conjugates with biogenic amines—spermine and spermidine, were synthesized from 3,11-dioxo analogs of fusidic acid and its methyl ester. Antitumor activity of the compounds was studied in vitro towards the 60 cell lines of nine different types of human tumors of the NCI collection. Introduction of pyrrolidine, n-butylamine, benzylamine, and ethylenediamine substituents into the molecules were found to provide a pronounced selective effect on five cell lines of leukemia: HL-60, K-562, MOLT-4, RPMI-8226, and SR, inhibiting their growth from 70% to complete death of cancer cells. Methylfusidate derivative with a spermine fragment was shown to exhibit the widest spectrum of antiproliferative action among the obtained compounds, inhibiting the growth of leukemia, NSC lung cancer, colon cancer, and melanoma cell lines of 68–92%.

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Acknowledgements

This work was financially supported by the Russian Foundation of Basic Research (research project No. 17-43-020021 r_a). The part of the research was carried out in accordance with federal program No. АААА-А19-119022290012-3. The structural studies of compounds (3)–(20) were carried out at the Center for Collective Use “Agidel” at the Institute of Petrochemistry and Catalysis, Russian Academy of Sciences. We thank National Cancer Institute for the screening of cytotoxicity of compounds 3–20.

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  1. Institute of Petrochemistry and Catalysis of Russian Academy of Sciences, 141 Prospect Oktyabrya, 450075, Ufa, Russian Federation

    Elena V. Salimova, Elena V. Tret’yakova & Lyudmila V. Parfenova

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  1. Elena V. Salimova
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  2. Elena V. Tret’yakova
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  3. Lyudmila V. Parfenova
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Correspondence to Elena V. Salimova.

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Salimova, E.V., Tret’yakova, E.V. & Parfenova, L.V. Synthesis and cytotoxic activity of 3-amino substituted fusidane triterpenoids. Med Chem Res 28, 2171–2183 (2019). https://doi.org/10.1007/s00044-019-02445-y

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