Programa de Pós-Graduação em Ciências Farmacêuticas

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  • Doctoral Thesis
    Caatinga em foco: conservação, quimiodiversidade e prospecção de compostos em cultivos controlados in vitro de Erythroxylum pungens O. E. Shulz (Erythroxylaceae)
    (Universidade Federal do Rio Grande do Norte, 2025-05-23) Moreira, Letícia Gondim Lambert; Giordani, Raquel Brandt; Fett Neto, Arthur Germano; https://orcid.org/0000-0001-5477-2610; http://lattes.cnpq.br/6760789832926234; http://lattes.cnpq.br/5032750980466610; https://orcid.org/0000-0001-8474-6077; http://lattes.cnpq.br/3046831133212359; Paula, Vanderlúcia Fonseca de; https://orcid.org/0000-0001-5860-194X; http://lattes.cnpq.br/7186193792162754; Konrath, Eduardo Luis; https://orcid.org/0000-0003-1838-4228; http://lattes.cnpq.br/6916587666283502; Voigt, Eduardo Luiz; https://orcid.org/0000-0003-0481-1129; http://lattes.cnpq.br/2455621187263790; Tavares, Emanuella de Aragão; https://orcid.org/0000-0003-4823-0211; http://lattes.cnpq.br/9967017709735330
    The Caatinga is recognized as one of the richest and most biodiverse Seasonally Dry Tropical Forests, standing out for its unique fauna and flora, which are well adapted to the peculiar conditions of this biome. Considered the most biodiverse semi–arid region in the world, its ecological and cultural importance in Brazil is vast, encompassing fields such as scientific research, arts, literature, and audiovisual productions. Understanding the impacts of climate change on the Caatinga is essential to support public policies and practices aimed at conservation and sustainable management, providing valuable insights to address the climatic challenges affecting the region. The preservation of this biome becomes even more urgent given that it is one of the least studied and most degraded by anthropogenic actions. Its conservation ensures the protection of species that have inhabited this region for centuries. Among them, Erythroxylum pungens O.E. Schulz stands out as an endemic plant predominantly found in the Seridó region of Rio Grande do Norte. In this study, the Caatinga is used as an artistic subject in the virtual exhibition entitled “Caatinga in Focus: Biodiversity, Science, and Preservation,” developed on a specific interactive platform for virtual tours. Additionally, a scientific review article was developed, focusing on the biotechnological potential of the Caatinga’s flora, highlighting the most studied secondary metabolites and exploring their technological and biotechnological applications in the development of new bioactive products. The research also examined the biosynthesis of tropane alkaloids over a 12–month developmental period of E. pungens, identifying compounds already reported in the literature and novel bioactive metabolites. In vitro callus cultivation was conducted using various culture media, with Gamborg B5 medium enriched with NAA (1–naphthaleneacetic acid) proving most effective for callus and adventitious root formation. Although other media produced larger calluses, adventitious roots did not form. Rapid oxidation impeded callus formation from leaves, as observed in similar species of the genus. Analytical results revealed traces of tropacocaine, along with indications of terpenoids, amino acids, and fatty acids. Findings were limited by low biomass yield, tissue injury, and slow growth, necessitating further studies to investigate the unique chemodiversity of the species. Lastly, the study evaluated the effects of stress–inducing agents on the species' cultures, analyzing the composition of tropane, indole alkaloids, and other bioactive compounds. Salicylic acid application led to the detection of N,N– dimethyltryptamine (N,N–DMT) in the roots after two days, while multifactorial tests involving high temperatures, water deficit, and high light exposure demonstrated a significant reduction in alkaloid concentration and diversity. These findings highlight the need for further investigation into the biochemical mechanisms and adaptive responses of E. pungens.
  • Master Thesis
    Alcaloides tropânicos de Erythroxylum pungens O. E. Shulz (Erythroxylaceae): do contexto edafoclimático da caatinga à investigação comportamental em Zebrafish (Danio rerio Hamilton)
    (Universidade Federal do Rio Grande do Norte, 2020-02-28) Moreira, Letícia Gondim Lambert; Giordani, Raquel Brandt; Luchiari, Ana Carolina; ; ; ; Andrade, Jean Paulo de; ; Menezes, Fabiano Peres; ; Ferreira, Leandro de Santis;
    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.