https://tede.unioeste.br/handle/tede/602 2026-06-10T12:04:34Z https://tede.unioeste.br/handle/tede/8435 Title: Estudo in silico de inibidores da glicogênio sintase quinase 3 beta (GSK-3beta) Autor: Ribeiro, Maira Primeiro orientador: Melo, Eduardo Borges de Abstract: Alzheimer's disease (AD) is the leading cause of dementia worldwide and is characterized by the accumulation of β-amyloid (Aβ) plaques and the formation of intracellular neurofibrillary tangles. The enzyme GSK-3β plays a central role in these processes, making it a promising target for the development of new therapies. Given the limitations of currently available treatments, computer-aided drug design (CADD) methodologies were employed, including Quantitative Structure–Activity Relationship (QSAR) modeling, 2D similarity-based virtual screening, and structure-based drug design approaches. QSAR models were developed from a dataset of 60 pyrazolone derivatives described as GSK-3β inhibitors. The models were generated using two different approaches: (i) based on SMILES representations (1D/2D descriptors, via AlvaDesc/OCHEM) and (ii) based on DFT-optimized structures (electronic, topological, and geometric descriptors, via Dragon 6.0). These approaches resulted in two main models: D1, containing 12 descriptors (R² = 0.908; Q²LOO = 0.855), and O1, containing 10 descriptors (R² = 0.874; Q²LOO = 0.808). Both models underwent internal and external validation, demonstrating robustness, statistical significance, and good predictive performance. 2D similarity-based virtual screening (performed using SwissSimilarity) yielded 9,343 compounds, which were subsequently reduced to 16 hits based on the Tanimoto coefficient. In parallel, molecular docking screening (performed with PyRx) led to the selection of 28 compounds, which were subjected to consensus docking (GOLD); among these, three were selected for molecular dynamics simulations. The QSAR models were applied to the compounds obtained from 2D similarity screening to predict their biological activity. Pharmacokinetic evaluation (performed using the BOILED-Egg model) of the 19 compounds selected in conjunction with the other analyses, the results reinforced the selection of two promising candidates, compound J and compound 7178171, both showing potential to permeate the blood–brain barrier. These results highlight the potential of in silico approaches for identifying promising GSK-3β inhibitors, contributing to the development of new therapeutic strategies for AD. Publisher: Universidade Estadual do Oeste do Paraná Tipo do documento: Dissertação 2026-03-04T00:00:00Z https://tede.unioeste.br/handle/tede/8316 Title: Produção de não-tecido por eletrofiação para análise de dissolução rápida de paracetamol em nanofibras de poli(1-vinilpirrolidona)-co-(acetato de vinila) Autor: Chang, Vanessa Rong Jen Primeiro orientador: Dragunski, Douglas Cardoso Abstract: The study investigates ways to improve the dissolution of paracetamol for patients with swallowing difficulties, using the sublingual administration of the drug in a non-woven format, which allows rapid release and avoids the need to swallow and chew. The electrospinning technique was applied to incorporate paracetamol (PCM) into the polymer poly(1-vinylpyrrolidone)-co-(vinyl acetate) (PVP/VA), which reduces the crystallinity of the drug, promoting an amorphous form of greater availability. The study included characterization of the electrospinning solution (viscosity and conductivity) and the resulting fibers, using scanning electron microscopy (SEM) for morphological analysis, Fourier transform infrared spectroscopy (FTIR) for identification of functional groups, differential scanning calorimetry DSC and Thermogravimetric analysis TGA for thermal properties, and X-ray diffraction (XRD) to evaluate crystallinity. The release test was performed on artificial saliva to check the dissolution time. Results indicate that higher concentration of PCM in fibers increases crystallinity, while lower concentrations result in amorphous fiber degrading more easily due to the disordered molecular state. Therefore, nonwovens with more concentrated PCM present the presence of crystallinity, as a result of the dissolution of PCM also promotes rapid dissolution of PCM in sublingual formulations, offering a promising alternative to improve the bioavailability of the drug and expanding its accessibility for patients with swallowing difficulties. Publisher: Universidade Estadual do Oeste do Paraná Tipo do documento: Dissertação 2025-03-07T00:00:00Z https://tede.unioeste.br/handle/tede/8306 Title: Avaliação da concentração de aciclovir em não-tecido eletrofiado de poli(1-vinilpirrolidona)-co-(acetato de vinila) para dissolução rápida Autor: Pfeifer, Gabriel das Neves Primeiro orientador: Dragunski, Douglas Cardoso Abstract: Herpes simplex virus (HSV), especially type 1 (HSV-1), is highly prevalent and causes recurrent orofacial infections. Acyclovir (ACV) is the standard treatment, but its low solubility limits bioavailability. Electrospinning enables the production of nanofibers with high surface area, enhancing rapid drug release. The PVP/VA copolymer combines hydrophilic and hydrophobic characteristics that aid in compound solubilization and transport, making it a promising matrix for drug‐delivery systems. However, few studies explore electrospun PVP/VA, and none apply ACV for topical use. This work develops and characterizes ACV-loaded PVP/VA nanofibers, evaluating their physicochemical and morphological properties and their potential for rapid release against HSV-1. FTIR analysis revealed interactions between ACV and PVP/VA, evidenced by shifts in the hydroxyl band. ACV increased fiber diameter but improved jet stability, as SEM analysis showed fewer beads. XRD indicated that ACV and PVP/VA do not form a fully homogeneous solid solution but likely a blend, since crystalline peaks remained detectable, although crystallinity was altered. DSC confirmed the disappearance of the ACV melting peak in polymer-containing samples. The release kinetics were best described by the Weibull model, with a diffusional mechanism (β < 1). Simulated dissolution showed complete solubilization of the electrospun material within 4 s, whereas pure ACV remained undissolved. Overall, the developed system is promising for rapid-release topical dressings or sublingual patches for HSV-1 treatment. Publisher: Universidade Estadual do Oeste do Paraná Tipo do documento: Dissertação 2025-12-03T00:00:00Z https://tede.unioeste.br/handle/tede/8227 Title: Uma revisão sobre o uso de adjuvantes na agricultura Autor: Meotti, Mauricio Luiz Primeiro orientador: Lindino, Cleber Antônio Abstract: The application of products in agricultural spraying has been widely used, as it aids in plant development in various ways, such as pest control and nutrition. However, to achieve good application efficiency, these products are not always easy to stabilize when used in mixtures, nor are they always compatible with each other, as they can form foam, cause losses during application, lack uniformity of contact with the plant, among other application problems. This work describes the types of adjuvants, their specific applications, the problems that mixtures of pesticides and fertilizers can cause and presents the main solutions. A literature review in scientific journal databases was conducted to evaluate the main research areas in the field, showing that there are numerous studies dispersed across different countries, with the authors of the research concentrated in the United States, Brazil, and China. It was also found that there are few patents filed or granted at the INPI (Brazilian National Institute of Industrial Property), indicating little concern for the intellectual property protection of products or processes produced in national companies. Publisher: Universidade Estadual do Oeste do Paraná Tipo do documento: Dissertação 2025-09-05T00:00:00Z