Alcaloides tropânicos de Erythroxylum pungens O. E. Shulz (Erythroxylaceae): do contexto edafoclimático da caatinga à investigação comportamental em Zebrafish (Danio rerio Hamilton)

Abstract

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of GC-MS spectroscopy analysis were 12 tropane alkaloids identified in this study, with three of these species and to unpublished alkaloid class.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.