Betulin derivatives impair Leishmania braziliensis viability and host-parasite interaction

W. Alcazar, A.S. López, Sami Alakurtti, Maija-Liisa Tuononen, J. Yli-Kauhaluoma, A. Ponte-Sucre

    Research output: Contribution to journalArticleScientificpeer-review

    7 Citations (Scopus)

    Abstract

    Leishmaniasis is a public health problem in tropical and subtropical areas of the world, including Venezuela. The incidence of treatment failure and the number of cases with Leishmania-HIV co-infection underscore the importance of developing alternative, economical and effective therapies against this disease. The work presented here analyzed whether terpenoids derived from betulin are active against New World Leishmania parasites. Initially we determined the concentration that inhibits the growth of these parasites by 50% or IC50, and subsequently evaluated the chemotactic effect of four compounds with leishmanicidal activity in the sub-micromolar and micromolar range. That is, we measured the migratory capacity of Leishmania (V.) braziliensis in the presence of increasing concentrations of compounds. Finally, we evaluated their cytotoxicity against the host cell and their effect on the infectivity of L. (V.) braziliensis. The results suggest that (1) compounds 14, 17, 18, 25 and 27 are active at concentrations lower than 10 µM; (2) compound 26 inhibits parasite growth with an IC50 lower than 1 µM; (3) compounds 18, 26 and 27 inhibit parasite migration at pico- to nanomolar concentrations, suggesting that they impair host-parasite interaction. None of the tested compounds was cytotoxic against J774.A1 macrophages thus indicating their potential as starting points to develop compounds that might affect parasite-host cell interaction, as well as being leishmanicidal.
    Original languageEnglish
    Pages (from-to)6220-6226
    JournalBioorganic & Medicinal Chemistry
    Volume22
    Issue number21
    DOIs
    Publication statusPublished - 2014
    MoE publication typeA1 Journal article-refereed

    Fingerprint

    Leishmania braziliensis
    Host-Parasite Interactions
    Parasites
    Derivatives
    Leishmania
    Inhibitory Concentration 50
    Venezuela
    Leishmaniasis
    Terpenes
    Growth
    Treatment Failure
    Coinfection
    Cell Communication
    HIV Infections
    Public Health
    Macrophages
    Public health
    Cytotoxicity
    Medical problems
    betulin

    Keywords

    • leishmania
    • betulin derivatives
    • host-parasite interaction
    • susceptibility

    Cite this

    Alcazar, W., López, A. S., Alakurtti, S., Tuononen, M-L., Yli-Kauhaluoma, J., & Ponte-Sucre, A. (2014). Betulin derivatives impair Leishmania braziliensis viability and host-parasite interaction. Bioorganic & Medicinal Chemistry, 22(21), 6220-6226. https://doi.org/10.1016/j.bmc.2014.08.023
    Alcazar, W. ; López, A.S. ; Alakurtti, Sami ; Tuononen, Maija-Liisa ; Yli-Kauhaluoma, J. ; Ponte-Sucre, A. / Betulin derivatives impair Leishmania braziliensis viability and host-parasite interaction. In: Bioorganic & Medicinal Chemistry. 2014 ; Vol. 22, No. 21. pp. 6220-6226.
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    title = "Betulin derivatives impair Leishmania braziliensis viability and host-parasite interaction",
    abstract = "Leishmaniasis is a public health problem in tropical and subtropical areas of the world, including Venezuela. The incidence of treatment failure and the number of cases with Leishmania-HIV co-infection underscore the importance of developing alternative, economical and effective therapies against this disease. The work presented here analyzed whether terpenoids derived from betulin are active against New World Leishmania parasites. Initially we determined the concentration that inhibits the growth of these parasites by 50{\%} or IC50, and subsequently evaluated the chemotactic effect of four compounds with leishmanicidal activity in the sub-micromolar and micromolar range. That is, we measured the migratory capacity of Leishmania (V.) braziliensis in the presence of increasing concentrations of compounds. Finally, we evaluated their cytotoxicity against the host cell and their effect on the infectivity of L. (V.) braziliensis. The results suggest that (1) compounds 14, 17, 18, 25 and 27 are active at concentrations lower than 10 µM; (2) compound 26 inhibits parasite growth with an IC50 lower than 1 µM; (3) compounds 18, 26 and 27 inhibit parasite migration at pico- to nanomolar concentrations, suggesting that they impair host-parasite interaction. None of the tested compounds was cytotoxic against J774.A1 macrophages thus indicating their potential as starting points to develop compounds that might affect parasite-host cell interaction, as well as being leishmanicidal.",
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    Alcazar, W, López, AS, Alakurtti, S, Tuononen, M-L, Yli-Kauhaluoma, J & Ponte-Sucre, A 2014, 'Betulin derivatives impair Leishmania braziliensis viability and host-parasite interaction', Bioorganic & Medicinal Chemistry, vol. 22, no. 21, pp. 6220-6226. https://doi.org/10.1016/j.bmc.2014.08.023

    Betulin derivatives impair Leishmania braziliensis viability and host-parasite interaction. / Alcazar, W.; López, A.S.; Alakurtti, Sami; Tuononen, Maija-Liisa; Yli-Kauhaluoma, J.; Ponte-Sucre, A.

    In: Bioorganic & Medicinal Chemistry, Vol. 22, No. 21, 2014, p. 6220-6226.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - Betulin derivatives impair Leishmania braziliensis viability and host-parasite interaction

    AU - Alcazar, W.

    AU - López, A.S.

    AU - Alakurtti, Sami

    AU - Tuononen, Maija-Liisa

    AU - Yli-Kauhaluoma, J.

    AU - Ponte-Sucre, A.

    PY - 2014

    Y1 - 2014

    N2 - Leishmaniasis is a public health problem in tropical and subtropical areas of the world, including Venezuela. The incidence of treatment failure and the number of cases with Leishmania-HIV co-infection underscore the importance of developing alternative, economical and effective therapies against this disease. The work presented here analyzed whether terpenoids derived from betulin are active against New World Leishmania parasites. Initially we determined the concentration that inhibits the growth of these parasites by 50% or IC50, and subsequently evaluated the chemotactic effect of four compounds with leishmanicidal activity in the sub-micromolar and micromolar range. That is, we measured the migratory capacity of Leishmania (V.) braziliensis in the presence of increasing concentrations of compounds. Finally, we evaluated their cytotoxicity against the host cell and their effect on the infectivity of L. (V.) braziliensis. The results suggest that (1) compounds 14, 17, 18, 25 and 27 are active at concentrations lower than 10 µM; (2) compound 26 inhibits parasite growth with an IC50 lower than 1 µM; (3) compounds 18, 26 and 27 inhibit parasite migration at pico- to nanomolar concentrations, suggesting that they impair host-parasite interaction. None of the tested compounds was cytotoxic against J774.A1 macrophages thus indicating their potential as starting points to develop compounds that might affect parasite-host cell interaction, as well as being leishmanicidal.

    AB - Leishmaniasis is a public health problem in tropical and subtropical areas of the world, including Venezuela. The incidence of treatment failure and the number of cases with Leishmania-HIV co-infection underscore the importance of developing alternative, economical and effective therapies against this disease. The work presented here analyzed whether terpenoids derived from betulin are active against New World Leishmania parasites. Initially we determined the concentration that inhibits the growth of these parasites by 50% or IC50, and subsequently evaluated the chemotactic effect of four compounds with leishmanicidal activity in the sub-micromolar and micromolar range. That is, we measured the migratory capacity of Leishmania (V.) braziliensis in the presence of increasing concentrations of compounds. Finally, we evaluated their cytotoxicity against the host cell and their effect on the infectivity of L. (V.) braziliensis. The results suggest that (1) compounds 14, 17, 18, 25 and 27 are active at concentrations lower than 10 µM; (2) compound 26 inhibits parasite growth with an IC50 lower than 1 µM; (3) compounds 18, 26 and 27 inhibit parasite migration at pico- to nanomolar concentrations, suggesting that they impair host-parasite interaction. None of the tested compounds was cytotoxic against J774.A1 macrophages thus indicating their potential as starting points to develop compounds that might affect parasite-host cell interaction, as well as being leishmanicidal.

    KW - leishmania

    KW - betulin derivatives

    KW - host-parasite interaction

    KW - susceptibility

    U2 - 10.1016/j.bmc.2014.08.023

    DO - 10.1016/j.bmc.2014.08.023

    M3 - Article

    VL - 22

    SP - 6220

    EP - 6226

    JO - Bioorganic & Medicinal Chemistry

    JF - Bioorganic & Medicinal Chemistry

    SN - 0968-0896

    IS - 21

    ER -

    Alcazar W, López AS, Alakurtti S, Tuononen M-L, Yli-Kauhaluoma J, Ponte-Sucre A. Betulin derivatives impair Leishmania braziliensis viability and host-parasite interaction. Bioorganic & Medicinal Chemistry. 2014;22(21):6220-6226. https://doi.org/10.1016/j.bmc.2014.08.023