https://repositorio.ufpb.br/jspui/handle/tede/5445 PPGPN 2026-04-06T06:32:20Z https://repositorio.ufpb.br/jspui/handle/123456789/37673 Título: Planejamento, síntese e avaliação do potencial antileishmania de novos 2-aminotiofeno-3-carboxamidas obtidas por modificação molecular Autor(es): Ferreira, Mirla Mirely Dantas Orientador: Mendonça Junior, Francisco Jaime Bezerra Abstract: Leishmaniasis is considered a public health problem, most of the cases are registered in emerging countries and in low-income populations, being still neglected tropical diseases which are not prioritized in research investments by large pharmaceutical companies, which results in few treatment options, in which they have several adverse effects, and long periods of treatment. In view of this, it became necessary to search for new effective and less toxic drugs, which is initiated by the understanding of Medicinal Chemistry, which allows the synthesis or isolation of better compounds. In addition, among the compounds with activity described in the literature, the 2-amino-thiophene derivatives are a versatile class of sulfur-containing compounds and an immense capacity to offer ligands for different molecular targets, with anti-leishmania potential. replacement of carbonitrile, which showed low solubility, by carboxamide at position-3, which showed activity against L. amazonenses in other studies. Thus, the objective of this work was to synthesize new 2-aminothiophene-3 carboxamide derivatives that are candidates for antileishmanial drugs, by carrying out the molecular modification of substituted 3-carbonitrile prototypes, in order to verify the importance of the substitution pattern of the C-3 position of the thiophene ring. Fifteen compounds were synthesized, with color varying between yellow and orange, yields from 20 to 98%, with the same synthetic route for all molecules. The compounds had their structures confirmed by NMR1H and 13C, their antileishmanial activities evaluated against the promastigote forms of Leishmania amazonensis, L. braziliensis, L. infantum and L. major, and their toxicities evaluated against RAW 264.7 macrophages. The 6BOC2 compound showed the highest inhibitory activity with IC50 values lower than 8μM for all species tested, and a selectivity index (SI) higher than 37.6. The comparison of the inhibition values and SI of the 3-carboxamide derivatives in relation to the 3- carbonitrile derivatives allows us to affirm that the presence of the 3-carbonitrile radical is not essential for antileishmanial activity. Although the substitution by the 3- carboxamide group did not result in compounds with activity superior to the 3- carbonitrile derivatives, obtaining new compounds with this substitution pattern should be taken into account when planning new antileishmanial drug candidates for this class of compounds. Editor: Universidade Federal da Paraíba Tipo: Dissertação 2022-03-28T00:00:00Z https://repositorio.ufpb.br/jspui/handle/123456789/37672 Título: Efeito antinociceptivo do geraniol (trans-3,7-dimetilocta-2,6-dien-1-ol) associado à codeína na região orofacial em camundongos Autor(es): Nunes, Ana Paula Lopes Orientador: Castro, Ricardo Dias de Abstract: The prospect of obtaining new alternatives for the pharmacological therapy of orofacial pain drives the investigation of products of natural origin with antinociceptive action associated with an opioid analgesic. Thus, the aim of this study was to investigate the activity of geraniol associated with codeine in the modulation of orofacial nociception, and possible depressant effect at the CNS level. This study is characterized as non- clinical, controlled and triple-blind. An experimental model of nociception in mice was adopted: formalin test,....For each test performed, six animals per group were treated, 30 minutes before the beginning of the experiment, by the intraperitoneal route (ip), according to the following experimental groups: a) geraniol 50 mg/kg + codeine 30 mg/kg; b) geraniol 50 mg/kg + codeine 15 mg/kg; c) geraniol 50 mg/kg + codeine 7.5 mg/kg; d) geraniol 50mg/kg; e) codeine 30 mg/kg (positive control); f) 0.9% sodium chloride (negative control). The analysis of the nociceptive behavior of the animals was performed after the injection of glutamate (20 μl, 25μM), capsaicin (20μl, 2.5μg) and formalin (20μl, 20%) in the right upper lip (paranasal) region of the animal. As a behavioral parameter, the time in seconds of friction of the referred region by the hind or front paws was considered. The results showed that in the glutamate test, geraniol and codeine in concentrations of 50 mg/kg and 30 mg/kg presented a reduction of 54.2% in the friction time, this same dose inhibited in 66.7% the nociception in the test of capsaicin (p<0.005). In the formalin test, the association at the same dose was able to reduce nociception by 86% (p<0.005). In order to investigate a possible myorelaxant and neurotoxic activity that could interfere with the results, the rota-rod test was also performed, where no such effects were observed. Therefore, from these experimental data, it can be suggested that there is a possible synergism of geraniol associated with codeine in orofacial antinociceptive activity. Editor: Universidade Federal da Paraíba Tipo: Dissertação 2021-06-08T00:00:00Z https://repositorio.ufpb.br/jspui/handle/123456789/37545 Título: Benzoatos e benzamidas 3,4,5-trisubstituídas: Avaliação antifúngica e tripanocida Autor(es): Nascimento, Lázaro Gomes Orientador: Sousa, Damião Pergentino de Abstract: Microbial and parasitic infections are a cause for concern worldwide because they are responsible for mortality and morbidity in a significant portion of the population, representing a serious threat to public health. Therefore, it is essential to search for new drug candidates for the treatment of these infections. Thus, in the present study, a collection of 20 synthetic analogues derived from gallic acid and 3,4,5-trimethoxybenzoic acid was prepared and a study was carried out against strains of the genus Candida and trypomastigote forms of Trypanosoma brucei. The Fischer and Schotten-Baumann esterification reactions were used to prepare the products, which were characterized by infrared spectroscopy, 1H NMR and 13C-APT. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) and the possible antifungal action mechanism of the compound with the best biological activity. 4- methylbenzyl gallate (10) with MIC of 0.11 mM against C. albicans ATCC 60193 and MIC of 0.06 mM against C. tropicalis ATCC 750 was the derivative with the greatest antifungal potency. In the investigation of the mechanism of action, it was observed that compounds 7 and 10 interact directly with ergosterol present in the plasma membrane or in the fungal cell wall, which shows that these structures are possible biological targets. In the antiparasitic evaluation, compounds 1-8 were evaluated in the viability test of the human myeloid cell line (HL-60) through the resuzarin reduction method. In the trypanocidal assay, the blood trypomastigote forms of T. brucei were used to determine the MIC and IC50 of these compounds. In general, analogues 3, 5 and 7 demonstrated better trypanocidal action against T. brucei, suggesting that substituents with three and four carbon side chains in linear arrangement increase the antiparasitic potency of gallates. The data demonstrate the pharmacological potential of these chemical classes and that they can be used as prototypes in future research aiming at the development of products with better trypanocidal and antifungal profiles. Editor: Universidade Federal da Paraíba Tipo: Tese 2025-05-28T00:00:00Z https://repositorio.ufpb.br/jspui/handle/123456789/37424 Título: Avaliação do perfil toxicológico in silico e in vivo de extratos da planta Cannabis sativa L. contendo os fitocanabinoides canabidiol e Δ9-tetraidrocanabinol Autor(es): Aquino, Débora Nascimento de Orientador: Diniz, Margareth de Fátima Formiga Melo Abstract: Cannabis sativa L., used for millennia for medicinal and industrial purposes, has a complex chemical composition, with particular emphasis on phytocannabinoids such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC). Despite advances in pharmacological research, gaps remain regarding the toxicity of full-spectrum extracts, which are essential to support their safe therapeutic use. This study aimed to evaluate the in silico toxicity of isolated Δ9-THC and CBD, as well as the acute toxicological profile of a full-spectrum extract enriched with Δ9-THC and CBD, identifying potential toxicity targets and contributing to a better understanding of their safety. For the in silico assessment, three computational tools were employed: ADMETsar, PASS online, and ProTox. The in silico results indicated acute oral toxicity classes III and IV for the chemical structures of Δ9-tetrahydrocannabinol and cannabidiol, respectively, according to the ADMETsar and ProTox analyses. Additionally, several toxicity endpoints were predicted, including respiratory toxicity, immunotoxicity, and ecotoxicity, among others. An acute oral toxicity test was conducted in an animal model following the OECD Guideline 423 (2001), using a single administration of 2000 mg/kg with a 14-day observation period. Pharmacological screening was performed, and parameters were monitored throughout the 14 days. After euthanasia, blood samples were collected for hematological and biochemical analyses. Macroscopic necropsy and histopathological examinations were also carried out. Regarding acute toxicity, no alterations were observed in hematological and histopathological parameters. The results demonstrate a favorable safety profile for the full-spectrum Cannabis sativa extract enriched with Δ9-THC and CBD, supporting its potential for controlled therapeutic applications. This research provides a scientific basis for the regulation of cannabis-based products in Brazil, contributing to clinical and regulatory decisionmaking by ANVISA. Editor: Universidade Federal da Paraíba Tipo: Tese 2025-08-26T00:00:00Z