Abstract
Pentavalent antimonials and amphotericin B remain as the main drugs to treat human leishmaniasis. However, the high toxicity and variable efficacy of treatment have stimulated the search for novel drug candidates. Naturally occurring alkaloids have a long history of antileishmanial activity. Here, we investigate the effects of the β-carboline-1-propionic acid alkaloid isolated from Quassia amara L., Simaroubaceae, against Leishmania amazonensis and Leishmania infatum. The alkaloid was isolated after liquid-liquid fractionation followed by chromatographic purification of the Q. amara methanol extract. The antileishmanial activity was evaluated by the microdilution method, using resazurin as the viability indicator. In addition, annexin and propidium iodide were used to detect parasites undergoing apoptosis. The anti-amastigote activity of the β-carboline-1-propionic acid alkaloid was determined by the infection of RAW 264.7 macrophages. The alkaloid displayed leishmanicidal activity against Leishmania amazonensis and L. infantum promastigotes and intracellular amastigotes with 50% inhibitory concentration ranging from 2.7 ± 0.82 to 9.4 ± 0.5 μg/ml and selectivity indexes >10. Moreover, apoptotic Leishmania amazonensis (19.5%) and L. infantum (40.4%) promastigotes were detected after 5 h incubation with the alkaloid. Finally, the β-carboline-1-propionic acid alkaloid inhibited the production of NO of infected macrophages, suggesting that the intracellular amastigote elimination occurs in a nitrosative stress-independent way. The results shown here suggest that the β-carboline-1-propionic acid alkaloid has potential as an antileishmanial agent.
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IAR and DSA designed the work. IAR wrote the manuscript. RSG and ARG performed the antileishmanial assays. ACFA, ICL and JDC performed the phytochemical assays and data analysis. RSG and HASS performed the apoptosis assay and data analysis. CMA performed the transmission electron microscopy. ABV and CSA critically revised the manuscript. All the authors have read the final manuscript and approved the submission.
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Gabriel, R.S., Amaral, A.C.F., Lima, I.C. et al. β-Carboline-1-propionic acid alkaloid: antileishmanial and cytotoxic effects. Rev. Bras. Farmacogn. 29, 755–762 (2019). https://doi.org/10.1016/j.bjp.2019.08.002
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DOI: https://doi.org/10.1016/j.bjp.2019.08.002