Project 3767: J. M. de Almeida, M. A. Mehmood, F. O. Nunes, L. F. Ceole, T. D. Klimeck, L. A. da Cruz, D. Tófoli, B. S. Borges, W. S. Garcez, I. A. Tozetti, L. C. Medeiros, F. R. Garcez, A. M. Ferreira. 2021. Synergistic effect and ultrastructural changes in Trypanosoma cruzi caused by isoobtusilactone A in short exposure of time. PLOS ONE. 16 (1):e0245882.
Specimen: Trypanosoma cruzi (unvouchered)
View: Scanning Electron Microscopy

Abstract

Butanolides have shown a variety of biological effects including anti-inflammatory, antibacterial, and antiprotozoal effects against certain strains of Trypanosoma cruzi. Considering the lack of an effective drug to treat T. cruzi infections and the prominent results obtained in literature with this class of lactones, we investigated the anti-T. cruzi activity of five butanolides isolated from two species of Lauraceae, Aiouea trinervis and Mezilaurus crassiramea. Initially, the activity of these compounds was evaluated on epimastigote forms of the parasite, after a treatment period of 4 h, followed by testing on amastigotes, trypomastigotes, and mammalian cells. Next, the synergistic effect of active butanolides against amastigotes was evaluated. Further, metacyclogenesis inhibition and infectivity assays were performed for the most active compound, followed by ultrastructural analysis of the treated amastigotes and trypomastigotes. Among the five butanolides studied, majoranolide and isoobtusilactone A were active against all forms of the parasite, with good selectivity indexes in Vero cells. Both butanolides were more active than the control drug against trypomastigote and epimastigote forms and also had a synergic effect on amastigotes. The most active compound, isoobtusilactone A, which showed activity against all tested strains inhibited metacyclogenesis and infection of new host cells. In addition, ultrastructural analysis revealed that this butanolide caused extensive damage to the mitochondria of both amastigotes and trypomastigotes, resulting in severe morphological changes in the infective forms of the parasite. Altogether, our results highlight the potential of butanolides against the etiologic agent of Chagas disease and the relevance of isoobtusilactone A as a strong anti-T. cruzi drug, affecting different events of the life cycle and all evolutionary forms of parasite after a short period of exposure.


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Article DOI: 10.1371/journal.pone.0245882

Project DOI: 10.7934/P3767, http://dx.doi.org/10.7934/P3767
This project contains
  • 98 Media
  • 1 Document
  • 1 Taxon
  • 1 Specimen
Total size of project's media files: 392.47M

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MorphoBank Project 3767
  • Creation Date:
    05 July 2020
  • Publication Date:
    13 January 2021
  • Project views: 7271

    Authors' Institutions

    • Universidade Federal de Mato Grosso do Sul (UFMS)

    • Instituto Carlos Chagas



    Members

    member name taxa specimens media media
    notes
    JULIO DE ALMEIDA
    Project Administrator
    119898
    Lia Carolina Soares Medeiros
    Observer
    0000
    Letícia Alves da Cruz
    Observer
    0000
    Inês Aparecida Tozetti
    Observer
    0000
    Tabata D’Maiella Freitas Klimeck
    Observer
    0000
    Ligia Fernanda Ceole
    Observer
    0000
    Felipe Oliveira Nunes
    Observer
    0000
    Fernanda Rodrigues Garcez
    Observer
    0000
    Beatriz Santana Borges
    Observer
    0000
    Walmir Silva Garcez
    Observer
    0000
    Alda Maria Teixeira Ferreira
    Full membership
    0000
    Danilo Tófoli
    Observer
    0000


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