DSpace Coleção:http://repositorio.ufc.br/handle/riufc/3032026-06-18T13:13:32Z2026-06-18T13:13:32ZProteína humana Cofilina-1: estudo plasmônico e eletroquímico do estado redox e da agregação induzida por oxidaçãoSouza, Luiz Henrique da Costahttp://repositorio.ufc.br/handle/riufc/867982026-06-17T12:20:49Z2025-01-01T00:00:00ZTítulo: Proteína humana Cofilina-1: estudo plasmônico e eletroquímico do estado redox e da agregação induzida por oxidação
Autor(es): Souza, Luiz Henrique da Costa
Abstract: The dysregulation of human cofilin-1 (CFL-1) protein is increasingly associated with the pathophysiology of neurodegenerative diseases. This pathogenicity is linked to cysteine oxidation mechanisms, which induce disulfide bond formation and confer toxic function, as well as to its intrinsic propensity for aggregation. Although physiological oxidants such as chlorotaurine (TauCl) are known to promote cellular stress, their specific role in inducing CFL-1 oligomers or aggregates remains unexplored. To address these gaps, this thesis aimed to monitor the redox state and interfacial aggregation kinetics of this protein in real-time. Initially, a platform on a gold substrate modified with 3-mercaptopropionic acid (MPA) and activated via EDC/NHS was developed for CFL-1 immobilization. Characterization was performed using surface plasmon resonance (SPR), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). This platform enabled the novel adaptation of the Ellman assay (DTNB) for a heterogeneous environment, with SPR monitoring. Results demonstrated that the immobilized protein predominantly maintained its native (reduced) conformation, presenting a stoichiometric ratio consistent with 4 free thiols per protein molecule at the interface. In the second phase, TauCl-induced CFL-1 aggregation kinetics were monitored in a novel manner via direct electrochemistry on screen-printed carbon electrodes (SPCEs). Using the intrinsic oxidation of tyrosine (Tyr) residues as a molecular marker, a time-dependent aggregation process was evidenced, manifested by a significant reduction in the anodic current. Aggregate formation was corroborated by complementary techniques, with DLS and AFM confirming increased hydrodynamic diameter and surface morphological changes, respectively. In conclusion, the developed platforms offer robust analytical tools for CFL-1 investigation. The SPR-based methodology offers perspectives for drug screening targeting specific redox forms of the protein, while the electrochemical approach elucidates redox state-dependent aggregation mechanisms, providing essential insights into the molecular bases of CFL-1-associated neurodegeneration.
Tipo: Tese2025-01-01T00:00:00ZEstudo racional de triterpenos do tipo lanostano como potenciais inibidores da proteína MYC: avaliação in silicoOliveira, José Augusto Carneiro dehttp://repositorio.ufc.br/handle/riufc/867112026-06-11T12:46:31Z2026-01-01T00:00:00ZTítulo: Estudo racional de triterpenos do tipo lanostano como potenciais inibidores da proteína MYC: avaliação in silico
Autor(es): Oliveira, José Augusto Carneiro de
Abstract: The MYC protein is one of the most investigated molecular targets for anticancer therapy. The structural characteristics of this intrinsically disordered protein have made inhibitor development a challenge. Lanostane-type triterpenes, such as pisosterol, are secondary metabolites constantly investigated for their anticancer activities. In this study, the anti-MYC potential of 821 lanostane-type triterpenes was investigated using ensemble docking, structural property prediction, pharmacokinetic parameters, molecular dynamics, and free energy calculation using the MM-GBSA method. As a result, the ligands (I-VIII) known as ganoderic acid E (I), ganoderlactone D (II), ganoderic acid Y (III), ganoderic acid Df (IV), lucidenic acid F (V), ganoderic acid XL4 (VI), mariessiic acid A (VII), and phellinol E (VIII) exhibited properties within the filters used. These eight ligands interacted with the molecular target, presenting interaction energies between -8.3 and -8.6 kcal.mol-1. In molecular dynamics, the RMSD, RMSF, radius of gyration, and hydrogen bonding plots revealed that ligands I, IV, VI, and VII interacted satisfactorily with the protein during the simulations, contributing to its conformational and energetic stabilization. The MYC-I and MYC-VII complexes presented free energies of -41.96 kcal.mol-1 and -44.98 kcal.mol-1, respectively. These results demonstrate that lanostane-type triterpenes were able to interact with MYC, forming stable complexes, suggesting that these molecules have the potential to inhibit the target
Tipo: Tese2026-01-01T00:00:00ZNanopartículas à base de quitosana e polietilenoglicol para encapsulamento do 5-fluorouracilPaiva Junior, José Ribamarhttp://repositorio.ufc.br/handle/riufc/864722026-05-26T12:17:35Z2025-01-01T00:00:00ZTítulo: Nanopartículas à base de quitosana e polietilenoglicol para encapsulamento do 5-fluorouracil
Autor(es): Paiva Junior, José Ribamar
Abstract: Cancer is becoming a serious threat to public health. Among non-communicable diseases, it is the most prevalent worldwide. Conventional cancer treatments include chemotherapy, radiotherapy, and, in more severe cases, surgery. Among the chemotherapeutic agents used, 5-fluorouracil is widely used in various types of cancer (colon, stomach, and others). However, it presents some problems, including a very short half-life, low bioavailability, and multiple side effects, including liver and kidney damage. Nanoencapsulation is an alternative to overcome these challenges. Nanoparticles (NPs) have excellent characteristics for controlled drug release
applications. They can be prepared using a variety of techniques, with ionotropic gelation being one of the most widely used. This combines oppositely charged polymers, with one of them acting as a cross-linking agent. Chitosan (CH) is a naturally occurring, positively charged polysaccharide extensively used in drug delivery systems. Tripolyphosphate (TPP) can be used
as a crosslinking agent to produce nanoparticles. Polyethylene glycol is a synthetic polymer that provides longer intravenous circulation time, better diffusion of NPs in tissue, and prevents interactions with other blood components, increasing the bioavailability of the encapsulated material. In this study, eight nanoparticle systems were developed: four without 5-FU and four
with 5-FU. The systems showed encapsulation efficiencies ranging from 9% to 28% and carrying capacities of 8.4% to 12.2%. The FTIR spectra of the systems displayed all the characteristic bands of the starting materials. The diameter of the nanoparticles without 5-FU ranged from 146 nm to 303 nm, and with 5-FU, it ranged from 187 nm to 396 nm. The release presented burst release, releasing approximately 55% within 48 hours of the assay, with release kinetics consistent with the diffusion mechanism model. Scanning electron microscopy
revealed that the nanoparticles had a spherical morphology. The PEG-containing systems did not exhibit significant interaction with the protein, suggesting a possible longer circulation time for intravenous administration. Cell viability, however, showed that encapsulated 5-FU was more effective against the HCT-116 cell line, with the systems CH/TPP/PEG14505-FU and
CH/TPP/PEG3350/5-FU being the most effective in the evaluations performed. The system CH/TPP/PEG1450/5-FU also demonstrated the emergence of encapsulated 5-FU against the MDA-MB-231 cell line, demonstrating great potential for anticancer applications.
Tipo: Tese2025-01-01T00:00:00ZHidrogéis via base de Schiff a partir de ciclodextrina e polissacarídeos modificados: veículos para curcuminaOliveira, Matheus Xavier dehttp://repositorio.ufc.br/handle/riufc/862402026-05-12T19:20:07Z2025-01-01T00:00:00ZTítulo: Hidrogéis via base de Schiff a partir de ciclodextrina e polissacarídeos modificados: veículos para curcumina
Autor(es): Oliveira, Matheus Xavier de
Abstract: Curcumin (CUR) is a polyphenol with anti-inflammatory, antioxidant, and antimicrobial properties; however, its application is limited due to its low solubility and stability under physiological conditions. To overcome these limitations, CUR was initially encapsulated in 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), forming 1:1 inclusion complexes with a high complexation constant (4.65 × 10³ at 25 °C). The use of ultrasound for 10 min (HP-CD/Cur10) increased solubility (from 0.42 to 156 µg mL−1) and stability (half-life from 281 to 2139 min), while also providing antibacterial activity against S. aureus MRSA, greater bioaccessibility, and biocompatibility. In the second stage, HP-CD/Cur10 was incorporated into a hydrogel composed of succinylated chitosan and oxidized cashew gum (GEL-50B), resulting in the GEL-Cur4 formulation, which showed a high curcumin content (440 µg mL−1), mechanical and thermal stability, as well as injectability, self-healing, and adhesiveness. CUR release demonstrated pH responsiveness, increasing intestinal bioaccessibility from 0.20 to 13.5% and enhancing antibacterial activity against K. pneumoniae (85% vs. 59% in the control). In an in vivo wound model, GEL-Cur4 accelerated healing (71% vs. 41% in the control) and positively modulated markers of inflammation and oxidative stress. Therefore, the novel system developed represents a promising multifunctional matrix for wound healing and oral curcumin delivery.
Tipo: Tese2025-01-01T00:00:00Z