http://repositorio.ufc.br/handle/riufc/303 2026-06-12T07:41:29Z http://repositorio.ufc.br/handle/riufc/86711 Título: 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: Tese 2026-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/86472 Título: 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: Tese 2025-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/86240 Título: 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: Tese 2025-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/86227 Título: Nanopartículas pH-responsivas de goma do cajueiro para terapia combinada contra o câncer Autor(es): Gomes, Raelle Ferreira Abstract: Cancer is a serious public health problem worldwide, and chemotherapy is considered the first-line approach in treating this disease. However, therapeutic effectiveness is limited by adverse events and the low bioavailability associated with chemotherapeutic agents. Combining two or more therapeutic agents represents an important strategy to enhance anticancer effects through synergistic actions and simultaneous accumulation in the tumor microenvironment. Polysaccharide-based pH-responsive prodrug nanocarriers show promise as co-delivery systems in cancer therapy. To demonstrate this, in this study, carboxymethyl cashew gum (CMCG) was successfully conjugated with curcumin (CUR) to form an acid-sensitive prodrug (CMCG-CUR). Paclitaxel (PTX) and resiquimod (R848) were then encapsulated in CMCG-CUR nanoparticles (CMCG-CUR/PTX and CMCG-CUR/R848) through non-covalent interactions. These nanoparticles were designed to promote the co-delivery of drugs to the tumor microenvironment. The structures of the prodrugs were confirmed by infrared spectroscopy and hydrogen nuclear magnetic resonance. Self-assembly into nanoparticles was observed using fluorescence spectroscopy, dynamic light scattering, and atomic force microscopy, indicating good dispersion and diameters below 200 nm. The drug loading values for CUR in the CMCG-CUR, CMCG-CUR/PTX, and CMCG-CUR/R848 nanoparticles were 7.0%, 3.0%, and 2.0%, respectively. The nanoparticles protected CUR from degradation and exhibited a controlled pH-responsive release profile. Furthermore, the CMCG-CUR and CMCG-CUR/PTX nanoparticles showed in vitro activity against CT-26 cells (murine colorectal carcinoma) and reduced cytotoxicity in non-tumor cells (RAW 264.7, murine macrophages), with a greater effect observed in the co-administration of CUR/PTX than the free drug. On the other hand, the CMCG-CUR/R848 nanoparticle showed no cytotoxicity in CT-26 cells but induced a proliferative effect in RAW 264.7 immune cells. The cell uptake study confirmed that the nanoparticles with CUR/PTX were absorbed by CT-26 cells, while those containing CUR/R848 were absorbed by RAW 264.7 cells. pH-responsive polysaccharide-based nanoparticles have shown promise for the selective and controlled co-delivery of drugs to the tumor microenvironment, with potential application in combination cancer therapies. Tipo: Tese 2026-01-01T00:00:00Z