Betulin derivatives impair Leishmania braziliensis viability and host-parasite interaction
| Autor: | Alicia Ponte-Sucre, Maija-Liisa Tuononen, Wilmer Alcazar, Adrian Silva López, Jari Yli-Kauhaluoma, Sami Alakurtti |
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| Rok vydání: | 2014 |
| Předmět: |
Clinical Biochemistry
Antiprotozoal Agents Pharmaceutical Science Leishmaniasis Cutaneous Biochemistry susceptibility Leishmania braziliensis Microbiology Cell Line Host-Parasite Interactions chemistry.chemical_compound Mice leishmania SDG 3 - Good Health and Well-being Drug Discovery medicine Parasite hosting Animals Humans Cytotoxicity Amastigote Molecular Biology Infectivity Betulin betulin derivatives biology Chemistry Macrophages Organic Chemistry Leishmaniasis medicine.disease biology.organism_classification Leishmania host-parasite interaction Triterpenes 3. Good health Immunology Molecular Medicine |
| Zdroj: | 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, vol. 22, no. 21, pp. 6220-6226 . https://doi.org/10.1016/j.bmc.2014.08.023 |
| ISSN: | 1464-3391 |
| DOI: | 10.1016/j.bmc.2014.08.023 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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