Programa de Pós-Graduação em Ciências Farmacêuticas
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Master Thesis Planejamento, síntese e avaliação biológica de hidrazonas e 1,2,3-triazóis(Universidade Federal do Rio Grande do Norte, 2024-02-29) Ferreira, Housemberg Donanvam da Silva; Jordão, Alessandro Kappel; Barbosa, Euzébio Guimarães; http://lattes.cnpq.br/3197108792266393; https://orcid.org/0000-0002-2920-3966; http://lattes.cnpq.br/2003461080025290; http://lattes.cnpq.br/1948445205661935; Gomes, Ana Paula Barreto; Gonzaga, Daniel Tadeu GomesHydrazones and triazoles comprise biologically active and synthetically viable chemical groups that are widely studied largely due to their extensive biological potential. Chapter one covers the entire synthesis process of 1,2,3-triazole compounds derived from amino acids, which, through four reaction steps starting from phenylalanine, resulted in the formation of five new compounds with yields between 22% and 55%. . From virtual screening studies, the possible biological activity of these compounds against the HCV virus, which causes hepatitis C, was verified. However, concrete experimental research data is still needed to prove this hypothesis. In the second chapter, the syntheses of hydrazonic compounds will be discussed starting from the drug isoniazid, where nine hydrazonic compounds were formed from reactions with different aromatic aldehydes with yields ranging from 25% to 92%. Based on virtual screening studies involving the hydrazones produced in this work, the hypothesis was formulated that these molecules have potential antineoplastic activity. Furthermore, due to the vast biological potential that these molecules present, the modulatory activity of antimicrobial resistance was evaluated based on evaluation of strains resistant to commercialized antimicrobials, and it was noted that the molecules produced in this work had a synergistic effect with the drugs studied in the tests, modulating the resistance of bacterial strains. However, additional tests will still be carried out to complete this study. In this work, a new synthetic step involving hydrazonic compounds was also investigated for the formation of their 4,5- dihydro-oxadiazole derivatives, obtaining a compound with a yield of 93%.Master Thesis Efeito da co-encapsulação do terpeno fitol nos parâmetro s físico-químicos de nanopartículas de ácido poli lático carregadas com metrotrexato(Universidade Federal do Rio Grande do Norte, 2021-08-27) Silva, Mariana Farias Alves da; Rocha, Hugo Alexandre de Oliveira; 0000-0003-2252-1221; http://lattes.cnpq.br/4651814546820796; http://lattes.cnpq.br/2593509584288129; http://lattes.cnpq.br/6498388348119206; Pedrosa, Matheus de Freitas Fernandes; http://lattes.cnpq.br/2929963416385218; Oshiro Júnior, João Augusto; http://lattes.cnpq.br/7718234509377672Cancer is the second leading cause of death in the world, surpassed only by cardiovascular disease. The lack of specificities of the drugs in the neoplastic tissue, makes the traditional cancer therapy subject to severe undesirable effects. Phytol is a secondary bioactive metabolite of chlorophyll and expresses a promising anticancer activity. Methotrexate is a chemotherapeutics commonly used in the treatment of malignant tumors. Nanoparticles have been studied for drug delivery in order to improve the targeting, enabling site-specific release, as well as overcoming limitations of biological barriers. This study mains the development and monitoring of coencapsulated nanoparticles loaded phytol and methotrexate and functionalized with polyethelineimine for potential increase in antiproliferative activity in cancer cells. The obtaining methodology used was nanoprecipitation with solvent evaporation. The composition and method parameters were evaluated by measurements of particle diameter, polydispersion index (PdI), zeta potential, pH, infrared absorption spectroscopy (FTIR-ATR), entrapment efficiency and performance indicators, including in vitro released, cell viability and stability studies. The conjugated nanoparticles presented average size around 200 nm (PdI <0.2) and the encapsulation efficiency was over 90% in the co-nanoencapsulated functionalized nanoparticles. Phytol was able to enable a slower and more controlled release in the conjugated nanoparticles. The samples were viable and with spherical morphology. The study promotes the development of a promising platform for co-encapsulated nanoparticles, for future tests of biological activity in vitro and in vivo.Master Thesis Estudo de associação de SNPs com a predisposição ao desenvolvimento de câncer de tireoide em pacientes da Liga Norte-Riograndense Contra o Câncer(2018-03-09) Santos, Isabelle Cristina Clemente dos; Silbiger, Vivian Nogueira; Genre, Julieta; ; ; ; Rezende, Adriana Augusto de; ; Uchoa, Adriana Ferreira; ; Santos, Edilmar de Moura;Thyroid cancer (CT) is the most common endocrine tumor and accounts for 1% of all malignancies. The number of cases diagnosed has been increasing and it is estimated that 212 thousand new cases will appear each year in the world. Currently, there is no study of genetic predisposition to CT performed in the admixture population of Rio Grande do Norte, a place where its incidence is high compared to the Brazilian average. In this way, the present project aims to evaluate the genetic predisposition of the local population to develop the CT, to better understand the pathophysiology of this disease and to establish potential biomarkers of predisposition. To this purpose, histopathological material was selected from the sample bank of the LNRCC Pathology Laboratory to compose the study group, and venous blood from donors from Hemovida blood bank as a control group. Genomic DNA from thyroid gland paraffin blocks and controls blood samples were extracted using the QIAamp® DNA FFPE Tissue kit and QIAamp® genomic DNA kit, respectively. The genotyping of a panel of 84 SNPs was performed using the MALDI-TOF Sequenom® MassARRAY iPLEX Gold Mass Spectrophotometer, in collaboration with the National Center for Genotyping of Santiago de Compostela - Spain. Thirty-six SNPs showed significant differences in their allelic frequencies when compared cases and controls. Of these, 23 SNPs were associated with risk of developing CT, mainly the variants rs2997312 (OR= 6,33), rs7024345 (OR= 2,97), rs10788123 (OR= 2,78), rs116909374 (OR= 3,40) and rs965513 (OR= 2,91) once they confer greater risk to patients. Additionally, 13 SNPs presented as a protective factor for the non-development of this neoplasia. Thus, the present study, unprecedented in the population of Rio Grande do Norte, suggests the association of these SNPs as biomarkers of CT predisposition in this population.