No abstract

The P38 MAPK protein is mainly involved in the synthesis of the proinflammatory cytokines IL1 and TNF-alpha and is important in the maintenance and amplification of the inflammatory process. Therefore, this protein presents high potential as a pharmacological target in the search for new treatments for inflammatory diseases. In silico approach has been of great importance to develop quick and inexpensive target identification and way to discover new bioactive molecules. This study used a computer ligand-docking method to screen the compounds from the Bahia semiarid region in silico for their ability to inhibit p38 MAPK activity. The protein crystallographic structure of the p38 MAPK was obtained from the Macromolecular Protein Data Bank. Northeast semiarid molecules were obtained from the ZINC database. The database was screened and a set of 233 molecules were selected as candidates using filtering based on parameters of the rule of Lipinski and Verber. The docking was carried out using the program Autodock Vina in its default configuration. The compound with ZINC databank code: 91596862 was found the most promising compound acoording to their binding free energy value obtained in the docking experiments (11,1 Kcal.mol-1) Intermolecular interactions analysis suggested that Van der Waals interactions are crucial to the ZINC molecule 69481892 in the active site of the p38 MAPK protein. Data resulting from all dockings are significant, although it has low accuracy. Thus, the hypothetical results of these in silico studies should be confirmed by in vitro and/or in vivo tests.

Primeiramente, agradeço a Deus que me guia em todas as situações e me dá forças para enfrentar os desafios da vida. Agradeço aos meus pais, Jucilene e Marcelino, por tudo! A torcida e apoio de vocês tem feito toda diferença. Agradeço a vocês por terem me ensinado tanto, que sem dúvidas foi o que me trouxe até aqui. Aos meus irmãos, Marcel, Itana e Lua por serem meus companheiros de vida e por toda cumplicidade. Aos meus sobrinhos Pedro e Benjamin e primos Júnior e Ana por me ensinar a dar valor ao que realmente importa e por, mesmo com a distância, serem a alegria do meu dia-a-dia. Agradeço também a toda minha família, tios, tias e avós, por todo incentivo e torcida. Ao meu orientador, Prof. Dr. José Eduardo Tanus dos Santos, pela orientação nesses dois anos de mestrado e pelo exemplo de competência e profissionalismo. Muito obrigada por acreditar e confiar em mim. Aos meus amigos e colaboradores, Grazi, Renato e Sandra por todo apoio e por nunca medir esforços para me auxiliar na execução deste trabalho. À Profª. Dr. Amedea Seabra e a Milena Pelegrino, por toda disponibilidade e colaboração para o desenvolvimento deste projeto.

According to the literature reports of both the sensory loss of individuals with type 2 Diabetes Mellitus and of the importance of family interrelationships in the management of this pathology, there is a demand to evaluate the sensory perception of relatives of individuals with type 2 Diabetes Mellitus. Consequently, the aim of this study was to evaluate sweet taste perception of diabetic individuals and their relatives. Methods: For this purpose, a sample of 150 volunteers was invited to participate, which was composed by individuals of both sexes, aged between 18 and 59 years, equally divided into three groups, constituted with 50 volunteers each: non-diabetic individuals, diabetic individuals and relatives. Furthermore, the glucose concentration of all participants was determined by capillary glycemia, and the diabetic participants were referred to a third-party laboratory to perform the glycated hemoglobin test using the immunoturbidimetric. Moreover, a questionnaire of personal and socio-demographic information was applied to diabetic participants and the sensory perception was evaluated through the test for sweet taste sensitivity. Results: The glycemic levels of the diabetic participants given by the Glycated Hemoglobin (HbA1c) test revealed that the results had a mean of 7.92 + 1.89%, equivalent to 180.60 + 54.52 mg/dL. The threshold was 3.34 g/L for diabetic participants, 2.60 g/L for relatives, and 1.92 g/L for the control group. Conclusions: Therefore, the present study demonstrated that the threshold index for sweet taste perception is higher in individuals with Type 2 Diabetes Mellitus and their relatives when compared to the control group.