masterThesis
Alcaloides tropânicos de Erythroxylum pungens O. E. Shulz (Erythroxylaceae): do contexto edafoclimático da caatinga à investigação comportamental em Zebrafish (Danio rerio Hamilton)
Fecha
2020-02-28Registro en:
MOREIRA, Letícia Gondim Lambert. Alcaloides tropânicos de Erythroxylum pungens O. E. Shulz (Erythroxylaceae): do contexto edafoclimático da caatinga à investigação comportamental em Zebrafish (Danio rerio Hamilton). 2020. 127f. Dissertação (Mestrado em Ciências Farmacêuticas) - Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, 2020.
Autor
Moreira, Letícia Gondim Lambert
Resumen
Brazilian biodiversity offers an enormous wealth of flora, a unique opportunity for
bioprospecting activity. Among the bioactive molecules found in most plant organisms,
alkaloids represent a wide variety of chemical structures. Among the Brazilian biomes, the
Caatinga, predominant vegetation in the Northeast region, offers biological heritage that cannot
be found anywhere else on the planet. It is in this xeric environment that Erythroxylum pungens
O.E Shulz is found, a tree-shrub species with great potential in little explored bioactive
alkaloids. The objective of this work is the bioprospecting of tropane alkaloids of Erythroxylum
pungens O.E Shulz, collected in a natural environment, the evaluation of the effect of water
stress on metabolism under young plants and the evaluation of the bioactive potential in vivo
in a Danio rerio (zebrafish) model organism, as well as, in silico analysis of the major alkaloid.
In Chapter 1, the water stress experiment was carried out by suspending irrigation in specimens
of E. Pungens in up to 20 days. We conclude that E. Pungens is able to store high levels of
proline, osmoregulatory and protective amino acid, in response to drought tolerance. Also, from
analysis by CG-MS, it was possible to observe that the production of tropane alkaloids is more
related to the development phase than to the water stress condition in which the plant was
subjected. In chapter 2 was identified by means of GC-MS spectroscopy analysis were 12
tropane alkaloids identified in this study, with three of these species and to unpublished alkaloid
class. Regarding toxicity, several teratogenic effects were observed at 5mg/L and the lethal dose
for zebrafish embryo was established at LC50 = 18,4 ± 1,7 µM/L. No mortality was observed in
adults, but a behavioral screen showed psychostimulatory action at 116,7 µM/L.. In silico,
targets involved in the antidepressant pathways were identified by docking with the alkaloid.
Overall, E. pungens is a source of unique tropane alkaloids, as the 3-(2-
methylbutyryloxy)tropan-6,7-diol, which seems to be involved in zebrafish behavioral changes
and deserve future investigation as a possible new molecule in the treatment of depressive-like
symptom or hallucinogens effects.