https://repositorio.ufpb.br/jspui/handle/tede/7029 PPGQ Sat, 27 Jun 2026 17:07:52 GMT 2026-06-27T17:07:52Z https://repositorio.ufpb.br/jspui/handle/123456789/38242 Título: Síntese de compostos bioativos via condensação de Knoevenagel e reações sequenciais utilizando quitosana como organocatalisador reciclável Autor(es): Abrantes, Paloma Gomes de Orientador: Vale, Juliana Alves Abstract: The Knoevenagel condensation reaction is a widely explored variant of aldol reactions, used to enhance the functionality of carbon chains in the search for new bioactive molecules. As it is a catalyst dependent process, the pursuit of innovative catalytic methodologies capable of promoting faster, more selective, and more efficient reactions has intensified. In this context, low molecular weight commercial chitosan (LWC) and EDTA-modified chitosan (LWC- EDTA-72h) were applied in the synthesis of 3-coumarin-carboxylic acids, Knoevenagel adducts derived from aromatic aldehydes or isatin, as well as xanthene and tetraketone derivatives. The obtained compounds were characterized by 1H and 13C NMR, melting point analysis, and evaluated for antileishmanial, antimicrobial, antitumor in vitro, and larvicidal activity against Aedes aegypti. LWC-EDTA-72h acted as a bifunctional heterogeneous organocatalyst at room temperature in reactions between aldehydes or isatins and malononitrile in ethanol:water (3:7, v/v), producing the desired adducts (1a–l and 2a–h) in 0.5–120 min with yields of 83–96%. The catalyst maintained its activity over six recovery and reuse cycles. In larvicidal assays, the Knoevenagel adducts 1c (R = 4-NO2) and 1g (R = 3-OCH3) exhibited LC50 values of 3.39 and 5.13 ppm, respectively, altering larval hemolymph without significant increases in nitric oxide (NO). As antimicrobials, 1a (R = H), 1f (R = 3-NO2), and 1h (R = 2- NO2) inhibited all evaluated strains (MIC = 512–1024 μg/mL). Against Leishmania infantum, the isatin-derived Knoevenagel adducts 2b (R = 5-Cl; R' = H), 2c (R = 5-Br; R' = H), and 2g (R = 5-CH3; R' = N-benzyl) showed IC50 values of 15.05, 18.38, and 12.7 μM (promastigote) and EC50 values of 5.74, 4.64, and 3.8 μM (axenic amastigote), with no cytotoxicity toward human erythrocytes. In PBMCs, they exhibited CC50 values of 25.2–34.41 μM, with SI values of 4.39– 7.42. No isatin-derived Knoevenagel adduct showed antimicrobial activity at the tested concentrations (2–1024 μg/mL). In the sequential synthesis of 3-coumarinocarboxylic acid 3a (R = H), commercial LWC was the most efficient catalyst in water or ethanol:water (3:7, v/v) at 75 °C, providing the product in short reaction times and good yields. With substituted salicylaldehydes, new coumarin derivatives (3b–i) were obtained in 10–45 min with yields of 77–88%, and up to four catalyst reuse cycles. Acids 3c–e, 3h, and 3i inhibited microbial growth from 1024 μg/mL, with compound 3d (R = 5-Br) being considered bactericidal and fungicidal. Xanthene (4a–g) and tetraketone (5a–g) derivatives were obtained through sequential reactions of aromatic aldehydes and dimedone (1:2 equivalents) in water at 75 °C using commercial LWC. The processes proved simple, sustainable, and efficient. Xanthene derivatives were obtained in 10–60 min (73–93%) and tetraketone in 10–20 min (82–94%), maintaining their structure and catalytic activity after six recycling cycles. In the biological assays, xanthene derivatives showed greater cytotoxicity than tetraketone. Compound 4f (R = 4-OH) was the most active (>94% inhibition) against chronic myeloid leukemia (K-562), human colon cancer (HCT-116), and lung carcinoma (A-549) cell lines, with IC50 values of 12.08, 6.61, and 5.54 μM, respectively, but exhibited high cytotoxicity toward non-tumor cells (MRC-5, 96.07%), resulting in a low SI. Nevertheless, it stands out as a lead compound for future modifications aiming at improved selectivity. Editor: Universidade Federal da Paraíba Tipo: Tese Wed, 22 Oct 2025 00:00:00 GMT https://repositorio.ufpb.br/jspui/handle/123456789/38242 2025-10-22T00:00:00Z https://repositorio.ufpb.br/jspui/handle/123456789/38236 Título: Desenvolvimento de testes para detecção da COVID-19 empregando análise multivariada em associação com espectrofluorimetria ou NIR portátil Autor(es): Gomes, Glaucio Jefferson Araújo Orientador: Lemos, Sherlan Guimarães Abstract: The outbreak of Coronavirus Disease (COVID-19) triggered a global health emergency, resulting in millions of deaths. During this period, efforts to control the spread of the virus and resume activities were significantly impacted by the availability of supplies and skilled labor necessary for accurately diagnosing the population. The challenges faced by many countries in conducting mass diagnostics through techniques such as RT-PCR highlight the ongoing need to seek alternative testing strategies that are effective, less reliant on high-cost raw materials, and scalable for widespread application. In this study, we explore the use of spectroscopic analysis of blood serum samples combined with multivariate analysis techniques for COVID-19 diagnosis. Two approaches were tested: the first using molecular fluorescence spectroscopy, and the second employing near- infrared spectroscopy with a portable device. In each approach, spectra from samples of patients with positive and negative COVID-19 diagnoses were obtained and used to train and validate classification models based on SIMCA, DD-SIMCA, PCA-DA, and PLS-DA modeling techniques. Among the tested approaches, analyses with excitation at 280 nm allowed the development of a PCA-DA classification model with a sensitivity of 0.98, selectivity of 0.84, and efficiency of 95%. This model demonstrated high efficiency in detecting seropositive samples, with only minor difficulty in classifying seronegative samples. In the analyses using excitation-emission matrix spectra, the DD-SIMCA model generated through PARAFAC decomposition best met the desired objectives, achieving an overall efficiency of 96%, sensitivity of 0.98, and selectivity of 0.92. Finally, a new method is presented for classifying blood serum samples as positive or negative for COVID-19 infection, using fluorescence spectroscopy analysis combined with multivariate analysis techniques. The use of spectroscopy in the analysis of serum samples proved to be effective in generating discrimination models that can be used to analyze new samples and determine whether the recorded signal is characteristic of a patient infected with SARS-CoV-2. The findings of this study proved to be promising and may contribute to the development of auxiliary diagnostic methods that are cost-effective, easy to perform, and provide rapid and reliable results. Editor: Universidade Federal da Paraíba Tipo: Tese Wed, 13 Nov 2024 00:00:00 GMT https://repositorio.ufpb.br/jspui/handle/123456789/38236 2024-11-13T00:00:00Z https://repositorio.ufpb.br/jspui/handle/123456789/38093 Título: Estudos quimioinformáticos de alcaloides de fabaceae: quimiotaxonomia, atividades biológicas e antileishamania Autor(es): Pontes, Adiel Henrique de Oliveira Orientador: Scotti, Marcus Tullius Abstract: Chemotaxonomy, a method of classifying organisms based on their chemical components, has proven to be a valuable tool in plant taxonomy. This strategy, combined with natural product analysis, can reveal information about the evolutionary relationships and ecological adaptations of plant species. In the Fabaceae (Leguminosae) family, known for its nitrogen-fixing ability and chemical diversity, chemotaxonomy has been particularly useful in clarifying taxonomic relationships. Alkaloids, an important group of natural products found in Fabaceae, often exhibit various biological activities, including anticancer properties. Self-organizing maps (SOMs) are a powerful analysis technique for visualizing and classifying complex datasets. By applying SOMs to the analysis of alkaloid profiles in Fabaceae, we can gain valuable insights into the chemical diversity of this family and identify potential chemotaxonomic markers. This approach can assist in the discovery of new bioactive compounds and enhance our understanding of the evolutionary history of Fabaceae. In this study, the application of SOMs demonstrated satisfactory results in the chemotaxonomic distinction of two genera of the Fabaceae family, Sophora and Erythrina, with accuracy rates exceeding 90% both overall and for each genus individually. In summary, it is possible to conclude that specific chemical structures may be related to different biosyntheses of secondary metabolites produced by plant species of these two genera, as well as specific biological activities of each genus. Furthermore, through the combination of molecular docking with the prediction of pharmacokinetic properties, it was possible to select three alkaloids from the initial database that present themselves as potential drugs against leishmaniasis. Editor: Universidade Federal da Paraíba Tipo: Dissertação Wed, 05 Mar 2025 00:00:00 GMT https://repositorio.ufpb.br/jspui/handle/123456789/38093 2025-03-05T00:00:00Z https://repositorio.ufpb.br/jspui/handle/123456789/37683 Título: Investigação do uso de solventes eutéticos profundos como co-catalisador na reação de Morita-Baylis-Hillman envolvendo derivados de isatina e ésteres acrílicos Autor(es): Andrade, Sandro Dutra de Orientador: Lima Junior, Claudio Gabriel Abstract: The search for greener synthetic protocols has been a challenge for Chemistry in recent decades. This work describes the use of Deep Eutectic Solvents (DES) as a substitute for volatile organic solvents and as a co-catalyst in the Morita-Baylis- Hillman Reaction (MBHR). We investigated some DES consisting of choline chloride (ChCl), glycerol (G), ethylene glycol (EG) and urea (U), applied in MBHR using as electrophiles, isatin, 5-chloroisatin, 5,7-dichloroisatin, 5- fluoroisatin, 5- nitro-isatin, 5-methyl-isatin and their respective N-alkylated derivatives. As Michael acceptors, acrylonitrile, methyl acrylate and 2-hydroxyethyl acrylate were used, and the experiments were conducted at room temperature, leading to obtaining twelve Morita-Baylis-Hillman adducts with yields that varied between 40 - 98%, in reactions lasting from 50 minutes to 30 hours, according to the type of DES and Michael acceptors used. The unpublished adducts derived from 2- hydroxyethyl acrylate (11 and 11a) were obtained during the investigations and completely characterized and elucidated by Infrared (IR) spectroscopic techniques, 1H and 13C Nuclear Magnetic Resonance and High Resolution Mass Spectrometry. We also sought to establish protocols reducing the amount of DABCO to catalytic proportions (15 mol%), in addition to a probable replacement with Hexamethylenetetramine (HMTA), which is less expensive and non- hygroscopic. In this case, even comparing their behavior by altering DES and Michael's acceptor, it was observed that the use of HMTA was not satisfactory in relation to DABCO. Throughout the investigation, we identified that the DES consisting of ChCl:EG (1:2) promoted a transesterification reaction with methyl acrylate, which made its use unfeasible as a solvent for reactions involving this Michael acceptor. New protocols were proposed for the synthesis of the adduct derived from 2-hydroxyethyl acrylate (11) using DESs constituted by ChCl:EG (1:2) and ChCl:U (1:2). The substitution of DES ChCl:EG (1:2) for ChCl:U (1:2) and the use of 50 mol% of DABCO proved to be a very promising methodology, reducing the reaction times (5 – 30h) in relation to other protocols established in the literature and satisfactory yields (45 - 95%). An investigation into the prototype reaction between N-methylisatin and methyl acrylate was carried out by Electrospray Mass Spectrometry (ESI(+)-MS), allowing to identify some reaction intermediates that are proposed in this work. The DES consisting of ChCl:U (1:2) was reused two more times, but the increased viscosity of the reaction medium proved to be a limiting factor to be overcome. Editor: Universidade Federal da Paraíba Tipo: Tese Fri, 10 Feb 2023 00:00:00 GMT https://repositorio.ufpb.br/jspui/handle/123456789/37683 2023-02-10T00:00:00Z