Heterocycle-fused lupane triterpenoids inhibit Leishmania donovani amastigotes

R Haavikko, A Nasereddin, N Sacerdoti-Sierra, D Kopelyanskiy, Sami Alakurtti, M Tikka, C L Jaffe, J Yli-Kauhaluoma (Corresponding Author)

    Research output: Contribution to journalArticleScientificpeer-review

    34 Citations (Scopus)

    Abstract

    The synthesis of heterocyclic betulin derivatives and their activity against Leishmania donovani is reported. Betulonic acid was used as a versatile intermediate. Several different fused heterocycles were introduced at the 2,3-position of the lupane skeleton including isoxazole, pyrazine, pyridine, indole and pyrazole rings. Also the 28-position was modified. Three compounds, 5, 8 and 25, showed low micromolar activity with IC50 values of 13.2, 4.3 and 7.2 µM, respectively. Compound 8 showed the best activity and selectivity, and its activity was tested on infected macrophages using a concentration, 5 µM, where no macrophage toxicity was exhibited. Interestingly, the activity of compound 8 on axenic amastigotes and Leishmania-infected macrophages was similar
    Original languageEnglish
    Pages (from-to)445-451
    Number of pages6
    JournalMedChemComm
    Volume5
    Issue number4
    DOIs
    Publication statusPublished - 2014
    MoE publication typeA1 Journal article-refereed

    Fingerprint

    Leishmania donovani
    Macrophages
    Isoxazoles
    Pyrazines
    Leishmania
    Skeleton
    Inhibitory Concentration 50
    Toxicity
    Derivatives
    lupane

    Cite this

    Haavikko, R., Nasereddin, A., Sacerdoti-Sierra, N., Kopelyanskiy, D., Alakurtti, S., Tikka, M., ... Yli-Kauhaluoma, J. (2014). Heterocycle-fused lupane triterpenoids inhibit Leishmania donovani amastigotes. MedChemComm, 5(4), 445-451. https://doi.org/10.1039/c3md00282a
    Haavikko, R ; Nasereddin, A ; Sacerdoti-Sierra, N ; Kopelyanskiy, D ; Alakurtti, Sami ; Tikka, M ; Jaffe, C L ; Yli-Kauhaluoma, J. / Heterocycle-fused lupane triterpenoids inhibit Leishmania donovani amastigotes. In: MedChemComm. 2014 ; Vol. 5, No. 4. pp. 445-451.
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    title = "Heterocycle-fused lupane triterpenoids inhibit Leishmania donovani amastigotes",
    abstract = "The synthesis of heterocyclic betulin derivatives and their activity against Leishmania donovani is reported. Betulonic acid was used as a versatile intermediate. Several different fused heterocycles were introduced at the 2,3-position of the lupane skeleton including isoxazole, pyrazine, pyridine, indole and pyrazole rings. Also the 28-position was modified. Three compounds, 5, 8 and 25, showed low micromolar activity with IC50 values of 13.2, 4.3 and 7.2 µM, respectively. Compound 8 showed the best activity and selectivity, and its activity was tested on infected macrophages using a concentration, 5 µM, where no macrophage toxicity was exhibited. Interestingly, the activity of compound 8 on axenic amastigotes and Leishmania-infected macrophages was similar",
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    Haavikko, R, Nasereddin, A, Sacerdoti-Sierra, N, Kopelyanskiy, D, Alakurtti, S, Tikka, M, Jaffe, CL & Yli-Kauhaluoma, J 2014, 'Heterocycle-fused lupane triterpenoids inhibit Leishmania donovani amastigotes', MedChemComm, vol. 5, no. 4, pp. 445-451. https://doi.org/10.1039/c3md00282a

    Heterocycle-fused lupane triterpenoids inhibit Leishmania donovani amastigotes. / Haavikko, R; Nasereddin, A; Sacerdoti-Sierra, N; Kopelyanskiy, D; Alakurtti, Sami; Tikka, M; Jaffe, C L; Yli-Kauhaluoma, J (Corresponding Author).

    In: MedChemComm, Vol. 5, No. 4, 2014, p. 445-451.

    Research output: Contribution to journalArticleScientificpeer-review

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    AU - Nasereddin, A

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    AU - Jaffe, C L

    AU - Yli-Kauhaluoma, J

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    AB - The synthesis of heterocyclic betulin derivatives and their activity against Leishmania donovani is reported. Betulonic acid was used as a versatile intermediate. Several different fused heterocycles were introduced at the 2,3-position of the lupane skeleton including isoxazole, pyrazine, pyridine, indole and pyrazole rings. Also the 28-position was modified. Three compounds, 5, 8 and 25, showed low micromolar activity with IC50 values of 13.2, 4.3 and 7.2 µM, respectively. Compound 8 showed the best activity and selectivity, and its activity was tested on infected macrophages using a concentration, 5 µM, where no macrophage toxicity was exhibited. Interestingly, the activity of compound 8 on axenic amastigotes and Leishmania-infected macrophages was similar

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    Haavikko R, Nasereddin A, Sacerdoti-Sierra N, Kopelyanskiy D, Alakurtti S, Tikka M et al. Heterocycle-fused lupane triterpenoids inhibit Leishmania donovani amastigotes. MedChemComm. 2014;5(4):445-451. https://doi.org/10.1039/c3md00282a