Erythroxylum pungens Tropane Alkaloids: GC-MS Analysis and the Bioactive Potential of 3-(2-methylbutyryloxy)tropan-6,7-diol in Zebrafish (Danio rerio)

Letícia Gondim Lambert Moreira; Maria Elisa Leite Ferreira; Fernanda Priscila Santos Reginaldo; Estela Mariana Guimarães Lourenço; José Angelo Silveira Zuanazzi; Euzébio Guimarães Barbosa; Leandro de Santis Ferreira; Arthur Germano Fett-Neto; Alberto José Cavalheiro; Ana Carolina Luchiari; Raquel Brandt Giordani

doi:10.1055/a-1264-4302

Planta Medica, Table of Contents

Planta Med 2021; 87(01/02): 177-186
DOI: 10.1055/a-1264-4302

Biological and Pharmacological Activities

Original Papers

Erythroxylum pungens Tropane Alkaloids: GC-MS Analysis and the Bioactive Potential of 3-(2-methylbutyryloxy)tropan-6,7-diol in Zebrafish (Danio rerio)

Letícia Gondim Lambert Moreira

¹Department of Pharmacy, Federal University of Rio Grande do Norte, Natal, RN, Brazil

,

Maria Elisa Leite Ferreira

²Department of Physiology and Behavior, Federal University of Rio Grande do Norte, Natal, RN, Brazil

,

Fernanda Priscila Santos Reginaldo

¹Department of Pharmacy, Federal University of Rio Grande do Norte, Natal, RN, Brazil

,

Estela Mariana Guimarães Lourenço

³Faculty of Pharmaceutical Sciences, Food and Nutrition, Federal University of Mato Grosso do Sul, Campo Grande, MS, Brazil

,

José Angelo Silveira Zuanazzi

⁴Faculty of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

,

Euzébio Guimarães Barbosa

¹Department of Pharmacy, Federal University of Rio Grande do Norte, Natal, RN, Brazil

,

Leandro de Santis Ferreira

¹Department of Pharmacy, Federal University of Rio Grande do Norte, Natal, RN, Brazil

,

Arthur Germano Fett-Neto

⁵Center for Biotechnology and Department of Botany, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

,

Alberto José Cavalheiro

⁶Chemistry Institute, São Paulo State University, Araraquara, SP, Brazil

,

Ana Carolina Luchiari

²Department of Physiology and Behavior, Federal University of Rio Grande do Norte, Natal, RN, Brazil

,

Raquel Brandt Giordani

¹Department of Pharmacy, Federal University of Rio Grande do Norte, Natal, RN, Brazil

› Author Affiliations

Abstract

Tropane alkaloids are specialized plant metabolites mostly found in the Erythroxylaceae and Solanaceae families. Although tropane alkaloids have a high degree of structural similarity because of the tropane ring, their pharmacological actions are quite distinct. Brazil is one of the main hotspots of Erythroxylum spp. diversity with 123 species (almost 66% of the species catalogued in tropical America). Erythroxylum pungens occurs in the Caatinga, a promising biome that provides bioactive compounds, including tropane alkaloids. As part of our efforts to investigate this species, 15 alkaloids in specimens harvested under different environmental conditions are presented herein. The occurrence of 3-(2-methylbutyryloxy)tropan-6,7-diol in the stem bark of plants growing in their natural habitat, greenhouse controlled conditions, and after a period of water restriction, suggests that it is a potential chemical marker for the species. This alkaloid was evaluated for several parameters in zebrafish (Danio rerio) as a model organism. Regarding toxicity, teratogenic effects were observed at 19.5 µM and the lethal dose for embryos was 18.4 µM. No mortality was observed in adults, but a behavioral screen showed psychostimulatory action at 116.7 µM. Overall, the alkaloid was able to cause zebrafish behavioral changes, prompting further investigation of its potential as a new molecule in the treatment of depression-like symptoms. In silico, targets involved in antidepressant pathways were identified by docking.

Key words

Erythroxylum pungens - Erythroxylaceae - tropane alkaloids - Danio rerio - Cyprinidae - Caatinga

Full Text

References

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