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Busca de produtos naturais como inibidores específicos de enzimas
(Universidade Federal de São Carlos, 2008-10-24) Severino, Richele Priscila; Vieira, Paulo Cezar; https://lattes.cnpq.br/8923844563320377; https://lattes.cnpq.br/8692556857906176
The present work describes the search of bioactive secondary metabolites isolated from plants, against enzymes: gGAPDH (glyceraldehydes-3- phosphate dehydrogenase from Trypanosoma cruzi and lysosomal cathepsins K, V, L and S. This work is divided in two parts: Part I: Study of the oil from the nut shells of Anacardium occidentale (Anacardiaceae) - Chagas disease, a parasitic infection caused by the flagellate protozoan Trypanosoma cruzi, is a major public health problem affecting millions of individuals in Latin America. On the basis of the essential role in the life cycle of T. cruzi, the enzyme gGAPDH has been considered an attractive target for the development of novel antitrypanosomatid agents. From the dicloromethane extract of A. occidentale were isolated phenolic compounds which were investigated on their inhibition activity against gGAPDH and trypomastigote forms of T. cruzi. The most promising compound was the 6-n-pentadecylsalicylic acid (AC1) with IC50 values of 28 μM against gGAPDH and 66.7 μg/mL against trypomastigote forms. In addition, a detailed mechanistic characterization of the effects of AC1 on the T. cruzi gGAPDHcatalyzed reaction showed clear noncompetitive inhibition with respect to both substrate G-3-P and cofactor NAD+. Part II: Study of natural products and synthetic derivatives searching for inhibitors of lysosomal cysteine peptidases - After completing the human genome, eleven lysosomal cysteine peptidases were identified. Those enzymes are involved in general protein degradation. The lysosomal cysteine peptidases are found in various tissues and those are found in many organs. Cathepsin K is associated to bone resorption, cathepsin L to skin cancer, at last cathepsins V and S are associated to the immune system. In this work, four enzymes (cathepsins K, V, L and S) were selected as a molecular target for the identification of new inhibitors. Some potent inhibitors of cathepsin V were found, and a study including kinetic characterization of the most potent inhibitors, including potency (IC50), mechanism of action and constant Ki was carried out. The most promising compound is the acridone alkaloid citbrasine (107), with values of IC50 of 1.2 μM and Ki of 0.24 μM. Moreover, it was determined that citbrasine is a competitive inhibitor against cathepsin V in relation to the substrate ZFRMCA. Additionally, it was carried out the study of molecular modeling for acridone alkaloids that showed significant inhibition of cathepsin V.
A gestão de recursos humanos no setor calçadista: o caso de Franca- SP
(Universidade Federal de São Carlos, 2008-10-24) Pitangui, Catarine Palmieri; Truzzi, Oswaldo Mário Serra; https://lattes.cnpq.br/5005536921435787
The present work approaches the Human Resource organizational practices that characterize the industrial footwear sector. And, specifically, looks a relation betwen the modernization of the management of the human resources and the size of the searched companies. For such, a explanatory research between companies of small, average and great sizes in the Franca-SP footwear industry, a region with great representation in the national industrial sector. This sector is little tied with the ample transformations of the capital. The low barriers to the entrance that this sector presents, allow that people with a cultural source decrease changed themselves into entrepreneurs. The perception of these actors is come back toward the production, for the world of the work in itself, and not for an administrative perception. And this reflects in all the industrial sizes of this industry. Through structuralized interviews applied to the entrepreneurs and/or to the RH management of the considered sample, it was possible to evidence a picture of practical enterprises that characterize the Franca-SP industry of footwear in this direction. The results disclose that the practical ones related to the management of the employees in the searched companies, in its majority, approach to the practical ones of Personal Department. In this sample, only in two of great size searched companies exists a RH functional area with practices more evolved for the people administration.