Synthesis and cytotoxic activity of 3-amino substituted fusidane triterpenoids
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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%.
KeywordsTriterpenoids Fusidic acid Fusidane amines Antitumor activity
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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Conflict of interest
The authors declare that they have no conflict of interest.
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