https://repositorio.ufpb.br/jspui/handle/tede/7029 PPGQ 2026-06-07T13:24:45Z 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 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 2023-02-10T00:00:00Z https://repositorio.ufpb.br/jspui/handle/123456789/37674 Título: Síntese, estudo in silico, elucidação teórica da estereoquímica e atividade antifúngica de novas imidas derivadas do safrol análogas à podofilotoxina Autor(es): Vilela, Raquel Finazzi Orientador: Athayde Filho, Petrônio Filgueiras de Abstract: Among nitrogenous compounds, imides represent important building blocks for the development of new drugs, considering that this class of compounds contains a wide range of biological activity, such as: antimicrobial, antitumor, anticonvulsant, antispamodic, analgesic, fungicide, bactericide, herbicide and more. In this sense, the aim of this study was to synthesize cyclic imide derivatives, from safrole, amino acid and aromatic amines substituted as podophyllotoxin analogues, which are substances known in the literature due to their extensive biological activity as antitumor, antiviral, antidepressant, among others, and that can be used in the microbiological combat of resistant strains, tumor cells and that present themselves as alternatives to commercial drugs, drugs available in the pharmaceutical market. In this research, ten molecules were synthesized, nine of which are new and characterized by Spectroscopy IV, 1H NMR, 13C NMR and High Resolution Mass Spectroscopy. In order to obtain the compounds, the isomerization of Safrol (1) was necessary, using Potassium Hydroxide (KOH), to obtain the Isosafrol isomer (2). After this step, isosafrole was reacted with maleic anhydride, to obtain the product (3). This was purified by means of a chromatographic column. After purification, compound (3) was used as an intermediate, subsequently reacting with p-substituted aromatic amines and two amino acids (glycine and p-aminobenzoic acid) to obtain the final products (4a- j) with yields around 60%. In silico studies showed that the compounds met Lipinski's parameters, suggesting good oral bioavailability, good absorption, moderate solubility, and drug-likeness values indicated that the compounds are frequently present in most drugs currently used in the OSIRIS Property program Explorer, showing strong to moderate antifungal activity against various strains of Candida and Cryptococcus. In the biological assay in particular, compounds 4b, 4c and 4h exhibited strong antifungal activity, with MICs between 0.17 - 0.73 μmol mL-1 . The compound 4j exhibited antifungal activity with MIC 1.28 μmol mL- 1 for all strains tested. In silico studies for the Lipinski's five rule have indicated that these compounds have potential candidates for new drugs. Oral bioavailability was assessed using these parameters. In addition, a computational study helped to attribute the stereochemistry of compound 4j, where the synthesized mixture is composed of two stereoisomers, 4j (SRR) and 4j (RSS). Editor: Universidade Federal da Paraíba Tipo: Tese 2020-05-29T00:00:00Z https://repositorio.ufpb.br/jspui/handle/123456789/37239 Título: Desenvolvimento e aplicação de protocolos de solvatação baseados em uma abordagem híbrida multiescala sequencial Autor(es): Silva, Daniel Gabriel da Orientador: Santana, Otávio Luís de Abstract: Describing the solvated phase remains a significant challenge, especially when the system contains protic and polar solvents, such as water, directly impacting the accuracy in predicting the properties of interest. This work aims to develop protocols that account for the effect of explicit solvation in the calculation of thermodynamic properties (especially Gibbs’ free energies), with the goal of reproducing experimental data within chemical accuracy, defined as an absolute error below 1 kcal mol-1. To achieve this, a multiscale hybrid approach was employed, characterized by the combination of simulation methods at different resolution levels: quantum mechanics, molecular mechanics, and implicit solvation models. As an evaluation metric, both theoretical and experimental reduction potentials of a set of redox reactions were considered. Although conceptually simple, modeling reduction potentials presents high operational complexity, particularly when aiming to achieve chemical accuracy. The methodological development involved the following steps: (i) performing a benchmark of reduction potentials in water using 25 density functionals; (ii) inclusion of explicit water molecules forming hydrogen bonds with the solute, incorporated into the reduction potential calculations; and (iii) inclusion of explicit water molecules in a solute-solvent ratio corresponding to the standard concentration (1 mol kg 1). The study − enabled the development of tools capable of automatically selecting solvent molecules in the vicinity of the modeled systems, positioned through classical molecular dynamics simulation procedures. These applications compose the suite named Solvate Suite. The results showed absolute mean errors ranging from 4.78 kcal mol-1 to 27.98 kcal mol-1 for the reduction potentials. However, this same methodology was also applied to the calculation of chemical shifts of 13C for a set of molecules from different categories, for which mean errors below 1.5 ppm were obtained. This performance enabled a more accurate prediction of the order of the peaks in the NMR spectrum of two isomeric carbohydrates, overcoming several incorrect assignments associated with the use of the implicit solvation model C-PCM. Editor: Universidade Federal da Paraíba Tipo: Tese 2025-06-30T00:00:00Z