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Planta Med 2020; 86(06): 425-433
DOI: 10.1055/a-1111-9566
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Anti-amoebic Activity of Leaf Extracts and Aporphine Alkaloids Obtained from Annona purpurea

César Díaz-Godínez‡
1   Department of Immunology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, México
,
Julio C. Ontiveros-Rodríguez‡
2   Consejo Nacional de Ciencia y Tecnología-Instituto de Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, México
,
Diana G. Ríos-Valencia
3   Department of Parasitology, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, México
,
José Enrique Herbert-Pucheta
4   Consejo Nacional de Ciencia y Tecnología-Laboratorio Nacional de Investigación y Servicio Agroalimentario y Forestal, Universidad Autónoma Chapingo, Chapingo, Estado de México, México
,
L. Gerardo Zepeda-Vallejo
5   Department of Organic Chemistry, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, México
,
Julio César Carrero
1   Department of Immunology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, México
› Author AffiliationsSupported by: Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (PAPIIT) 20170808, 20180092 and 20194908
Supported by: Institutional program “Nuevas alternativas para el tratamiento de enfermedades infecciosas” (NUATEI)
Supported by: Consejo Nacional de Ciencia y Tecnología 284830, INFRA-269012
Supported by: Secretaría de Investigación y Posgrado-IPN 20170808, 20180092 and 20194908
Further Information

Publication History

received 06 August 2019
revised 17 January 2020

accepted 26 January 2020

Publication Date:
27 February 2020 (online)

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Abstract

Annona purpurea has been traditionally used by indigenous and socioeconomically disadvantaged people to treat infectious and parasitic diseases, including amoebiasis. The goal of this study was to assess the effect of a crude methanolic extract, an alkaloid extract, and aporphine alkaloids from leaves of A. purpurea on the viability of Entamoeba histolytica trophozoite cultures and to identify the mechanism of action. Different concentrations of the extracts and alkaloids purpureine (1), 3-hydroxyglaucine (2), norpurpureine (3) glaziovine (4), and oxopurpureine (5) were added to the cultures, and dead parasites were counted after 24 h using a tetrazolium dye reduction assay and analyzed by flow cytometry. The crude extract did not affect the viability of amoebae, but the alkaloid extract and the derived alkaloid glaziovine (4) had important anti-amoebic activity with an IC50 of 33.5 µM compared to that shown by metronidazole (6.8 µM). The treatments induced significant morphological changes in the trophozoites, and most parasites killed by the alkaloid extract were positive for Annexin V, suggesting that apoptosis was the main mechanism of action. In contrast, glaziovine (4) induced less apoptosis with more amoebic lysis. This study supports the idea that aporphine alkaloids from A. purpurea, mainly (+)-(R)-glaziovine (4), could contribute to the development of new formulations for the treatment of amoebiasis. In addition, X-ray diffraction structural analysis and complete 1H and 13C NMR assignments of (+)-(R)-glaziovine (4) were performed and reported for the first time.

Key words

Entamoeba histolytica - Annona purpurea - Annonaceae - aporphine alkaloids - glaziovine - anti-amoebic

Supporting Information

    The mono- and bidimensional NMR spectra of (+)-(R)-glaziovine (4), its X-ray crystallographic information, and the dose-response curves that support IC50 calculation values of the alkaloids are available as Supporting Information.

  • Supporting Information
 

  • References

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