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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
1   Department of Pharmacy, Federal University of Rio Grande do Norte, Natal, RN, Brazil
,
Maria Elisa Leite Ferreira
2   Department of Physiology and Behavior, Federal University of Rio Grande do Norte, Natal, RN, Brazil
,
Fernanda Priscila Santos Reginaldo
1   Department of Pharmacy, Federal University of Rio Grande do Norte, Natal, RN, Brazil
,
Estela Mariana Guimarães Lourenço
3   Faculty of Pharmaceutical Sciences, Food and Nutrition, Federal University of Mato Grosso do Sul, Campo Grande, MS, Brazil
,
José Angelo Silveira Zuanazzi
4   Faculty of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
,
Euzébio Guimarães Barbosa
1   Department of Pharmacy, Federal University of Rio Grande do Norte, Natal, RN, Brazil
,
Leandro de Santis Ferreira 
1   Department of Pharmacy, Federal University of Rio Grande do Norte, Natal, RN, Brazil
,
Arthur Germano Fett-Neto
5   Center for Biotechnology and Department of Botany, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
,
Alberto José Cavalheiro
6   Chemistry Institute, São Paulo State University, Araraquara, SP, Brazil
,
Ana Carolina Luchiari
2   Department of Physiology and Behavior, Federal University of Rio Grande do Norte, Natal, RN, Brazil
,
Raquel Brandt Giordani 
1   Department of Pharmacy, Federal University of Rio Grande do Norte, Natal, RN, Brazil
› Author AffiliationsSupported by: Fundação de Amparo à Pesquisa do Estado de São Paulo FAPESP/INCTBioNat 2014/50926-0
Supported by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Finance code 001
Supported by: Conselho Nacional de Desenvolvimento Científico e Tecnológico 445149/2014-0
Supported by: Conselho Nacional de Desenvolvimento Científico e Tecnológico INCT BioNat 465637/2014
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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

Supporting Information

    Mass spectra of alkaloids (Figs. 1S–15S) tentatively identified in E. pungens in their natural habitat and cultivated in a greenhouse (Figs. 16S and 17S), GC-MS profile of E. pungens cultivated (Fig. 19S) and wild species (Fig. 18S), a ranking of the top 25 in silico results regarding biological targets (Fig. 20S), tables with a structure-based strategy (Table 1S) and ligand-based in silico approach (Table 2S) are available in the Supporting Information.

  • Supporting Information


Publication History

Received: 28 March 2020

Accepted after revision: 16 September 2020

Article published online:
11 November 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
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