https://repositorio.ufu.br/handle/123456789/5496 Fri, 18 Sep 2026 03:42:29 GMT 2026-09-18T03:42:29Z https://repositorio.ufu.br/handle/123456789/50275 Title: Contribuições à Toxinologia de Formigas do Cerrado pela caracterização e bioprospecção de suas peçonhas e moléculas - uma abordagem experimental e in silico Abstract: Animal venoms are an established source of drugs, yet the field concentrates on snakes, scorpions and spiders, while ants, the richest lineage of venomous animals, remain underexplored, constrained by minute venom yields and by the gap between the abundance of omics data and the confirmed function of the molecules. The general aim of this thesis was to characterize and bioprospect the biotechnological and therapeutic potential of the venoms of Cerrado ants (and of their associated molecules and symbionts) through an integrated, experimental and in silico approach. Organized as a compilation of ten articles, it comprises three foundational reviews (methods in toxinology; the Brazilian contribution to ant toxinology; the ant microbiome), two systematic reviews on value and translation (the animal-toxin patent landscape; conservation as a bioeconomic strategy under the access-and-benefit-sharing regime), two experimental characterization studies, one computational study and two therapeutic-validation studies. Methods spanned biochemical, enzymatic and functional venom assays, mass spectrometry, a bioinformatics pipeline for sequence-based function prediction, and in vitro and in vivo assays of antimicrobial, immunomodulatory, antinociceptive and safety endpoints. Key results include the first toxinological characterizations of Neoponera foetida and Odontomachus haematodus, two Cerrado Ponerinae whose enzymatically rich venoms differ in function according to each species' ecology; an in silico pipeline that prioritized Hymenoptera peptides and highlighted ant dinoponeratoxins and ponericins as selective candidates; and the demonstration that the monomerized, non-lytic ectatomin subunits ET1A and ET1B are bactericidal against multidrug-resistant strains, restrain neutrophil extracellular trap formation without cytotoxicity, show antinociceptive potential in Drosophila melanogaster larvae, and are safe in the chick-embryo model. We conclude that Cerrado ant venoms are a promising source of bioactive molecules, that integrating experimental and computational approaches accelerates their discovery in neglected taxa, and that the resulting economic value may constitute an argument for biodiversity conservation. Fri, 21 Aug 2026 00:00:00 GMT https://repositorio.ufu.br/handle/123456789/50275 2026-08-21T00:00:00Z https://repositorio.ufu.br/handle/123456789/50262 Title: Modelagem e docking molecular de Derlin-1: ligantes naturais e modulação do estresse do retículo endoplasmático em células de câncer de próstata Abstract: The endoplasmic reticulum (ER) plays a central role in protein synthesis, folding, and quality control. Its homeostasis is maintained by the Unfolded Protein Response and Endoplasmic Reticulum-Associated Degradation pathways, the latter being responsible for the retrotranslocation and degradation of misfolded proteins. Derlin-1 acts as a key component of the retrotranslocation channel in association with the p97/VCP ATPase, being activated by high protein demand. Accordingly, its overexpression has been described in different tumors, including prostate cancer (PCa), in which a strong dependence on proteostasis mechanisms is observed, especially in castration-resistant prostate cancer (CRPC). Indeed, in CRPC there is intense metabolic reprogramming and persistent activation of ER stress, such that Derlin-1 helps sustain transformed cells. In this scenario, the pharmacological modulation of Derlin-1 has proven to be a still poorly explored therapeutic strategy. Natural compounds are historically relevant, especially in oncology, and structural bioinformatics tools, such as homology modeling, docking, and molecular dynamics, combined with ADMET predictions, allow for the rational investigation of their interaction with ligands. Thus, this theoretical framework positions Derlin-1 as a relevant molecular target and explores the phenolic compound 4-nerolidylcatechol as a bioactive and structurally compatible natural candidate for modeling and molecular docking approaches aimed at CRPC. Mon, 31 Aug 2026 00:00:00 GMT https://repositorio.ufu.br/handle/123456789/50262 2026-08-31T00:00:00Z https://repositorio.ufu.br/handle/123456789/49714 Title: Efeitos de extratos e compostos biologicamente ativos no controle de células tumorais mamárias Abstract: Breast cancer (BC) is the most commonly diagnosed malignant neoplasm worldwide, representing a major public health concern. Its origin occurs predominantly in the cells of the terminal duct lobular unit of the breast and may exhibit a luminal phenotype characterized by the expression of hormone receptors. In estrogen receptor (ER)-positive tumors, endocrine therapy is one of the main therapeutic strategies, targeting estrogen signaling and resulting in significant improvements in patient survival. However, resistance to endocrine therapy remains one of the major challenges in the treatment of ER-positive breast cancer, significantly compromising prognosis and contributing to disease progression. In this context, phytoestrogens have emerged as biologically active plant-derived compounds capable of interacting with estrogen receptors and modulating several pathways involved in cell proliferation and survival. This review summarizes the main phytoestrogens and other natural compounds structurally similar to 17β-estradiol, with emphasis on their mechanisms of action and effects described in ER-positive breast tumor cells. Thus, this study aims to discuss the potential of these compounds as adjuvant agents or candidates for further investigation in the development of novel therapeutic strategies for breast cancer resistant to endocrine therapy. Mon, 05 Dec 2022 00:00:00 GMT https://repositorio.ufu.br/handle/123456789/49714 2022-12-05T00:00:00Z https://repositorio.ufu.br/handle/123456789/48705 Title: Aplicações translacionais de Drosophila melanogaster em neurociência: mecanismos moleculares, modelos de doenças e investigação terapêutica Abstract: This thesis investigated the translational applications of Drosophila melanogaster in neuroscience through studies focused on neurodegeneration and nociception. In the first study, metabolic and peptide fractions derived from kefir were evaluated in amyloidogenic models of Alzheimer’s disease in D. melanogaster and in cell culture. The biomolecules were investigated using biochemical, in vitro, and in vivo approaches. The results demonstrated the neuroprotective potential of the kefir-derived fractions, including attenuation of neurodegenerative phenotypes, improvement of oxidative parameters, and reduction of neurodegeneration-associated alterations in the experimental models. In the second study, a voltage-gated sodium channel mutant model in D. melanogaster was validated as an experimental tool for investigating mechanisms related to nociception and chronic pain. Using this model, the modulatory potential of cannabidiol (CBD) on nociceptive parameters and conserved neural pathways associated with pain signaling was evaluated. Collectively, the findings reinforce the translational relevance of D. melanogaster as a model organism in neuroscience, highlighting its applicability in the investigation of conserved molecular mechanisms, the experimental modeling of neurological diseases, and the prospecting of therapeutic strategies with neuroprotective and analgesic potential. Fri, 20 Feb 2026 00:00:00 GMT https://repositorio.ufu.br/handle/123456789/48705 2026-02-20T00:00:00Z