https://tede.unioeste.br/handle/tede/602 Mon, 24 Aug 2026 12:52:15 GMT 2026-08-24T12:52:15Z https://tede.unioeste.br/handle/tede/8617 Title: Construção de modelos de predição Qsa(P)R com objetivos ambientais e toxicológicos Autor: Silva, Natalya Aline Barros Ribeiro da Primeiro orientador: Melo, Eduardo Borges de Abstract: This dissertation aimed to develop QSAR (Quantitative Structure–Activity Relationship) and QSPR (Quantitative Structure–Property Relationship) predictive models for the assessment of toxicological and environmental properties of organic compounds of regulatory interest. The study focused on three main groups of compounds: per- and polyfluoroalkyl substances (PFAS), pesticides classified as persistent organic pollutants (POPs), and substituted diphenyl ethers, including polymethoxylated, polyhydroxylated, methoxylated polychlorinated, and hydroxylated polychlorinated derivatives. The environmental persistence, high mobility, and toxic potential of these substances highlight the need for computational tools capable of supporting risk assessment in a rapid, reliable manner while reducing the dependence on experimental testing. The first study aimed to develop QSAR models to predict oral and inhalation toxicity parameters of PFAS in rats and mice using two-dimensional molecular descriptors and partial least squares (PLS) regression. The second study focused on developing QSAR models based on partial least squares discriminant analysis (PLS-DA) to classify the contact toxicity of pesticides toward honeybees (Apis mellifera), enabling the identification of structural patterns associated with the ecotoxicological potential of these compounds. The third study consisted of developing QSPR models to predict the soil organic carbon sorption coefficient (LogKoc) of substituted diphenyl ethers. Different algorithms for estimating LogP and LogS descriptors were compared, and the application of a hybrid descriptor (LogSp), obtained by combining lipophilicity and water solubility, was evaluated. The results demonstrated that LogP-based descriptors exhibited superior predictive performance, with the MLOGP algorithm showing the best performance among the theoretical methods evaluated. Furthermore, models developed using the hybrid Original_LogSp descriptor outperformed those based solely on individual descriptors, demonstrating that the combination of lipophilicity and water solubility improves the representation of physicochemical properties associated with soil sorption. The developed models exhibited satisfactory statistical robustness, stability, and high predictive performance, meeting the recommended validation criteria for QSAR/QSPR studies. The results demonstrate the potential of these computational approaches as valuable tools for toxicological and environmental assessment, contributing to the understanding of the molecular mechanisms underlying toxicity, mobility, and persistence of organic contaminants. Therefore, this dissertation provides predictive models that can support risk assessment, chemical regulation, and the development of safer compounds while reducing the need for experimental testing and promoting more sustainable strategies for protecting human health and the environment. Publisher: Universidade Estadual do Oeste do Paraná Tipo do documento: Dissertação Wed, 03 Jun 2026 00:00:00 GMT https://tede.unioeste.br/handle/tede/8617 2026-06-03T00:00:00Z https://tede.unioeste.br/handle/tede/8594 Title: Síntese e obtenção de catalisador à base de vidro soda-cálcico funcionalizado com NaOH para reações de transesterificação na produção de biodiesel e despolimerização do PET em PTA Autor: Moreira, Luis Carlos Fagundes Primeiro orientador: Schneider, Ricardo Abstract: This study aimed to develop and evaluate heterogeneous catalysts produced from recyclable soda-lime vitreous waste, combined with eggshells and NaOH, for application in two environmentally relevant chemical pathways: the transesterification of vegetable oils for biodiesel production and the depolymerization of polyethylene terephthalate (PET) to obtain terephthalic acid (PTA). The proposal is based on the valorization of municipal solid waste through its transformation into sustainable catalytic materials, aligned with the principles of green chemistry and the circular economy. The samples were characterized using various analytical techniques, including Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, laser-induced optical emission spectroscopy (LIBS), X-ray diffraction (XRD), and particle size analysis by laser scattering. The results of these analyses confirmed significant structural and chemical changes in the glass matrix, such as the presence of hydroxylated groups, modification of the silicate network, the elimination of carbonates, and the incorporation of elements such as sodium and calcium, which are directly associated with catalytic activity in basic reactions. Particle size analysis, through statistical analysis of the data, confirmed the good uniformity in sphere size, validating the methodology used in their manufacture. In the catalytic tests, we obtained a 60% methyl ester content in the production of biodiesel from the transesterification of soybean oil, and conversions exceeding 70% in the depolymerization of PET for PTA recovery, even under moderate operating conditions. These results highlight the potential of the developed catalysts as substitutes for conventional catalysts. Future studies aimed at improving their physicochemical properties, as well as optimizing reaction parameters and conditions, could increase their catalytic efficiency. Publisher: Universidade Estadual do Oeste do Paraná Tipo do documento: Dissertação Mon, 29 Jun 2026 00:00:00 GMT https://tede.unioeste.br/handle/tede/8594 2026-06-29T00:00:00Z 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 Wed, 04 Mar 2026 00:00:00 GMT https://tede.unioeste.br/handle/tede/8435 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 Fri, 07 Mar 2025 00:00:00 GMT https://tede.unioeste.br/handle/tede/8316 2025-03-07T00:00:00Z