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| Author(s): |
Gustavo Henrique Goulart Trossini
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) |
| Defense date: | 2004-04-16 |
| Examining board members: |
Elizabeth Igne Ferreira;
Chung Man Chin;
Leoberto Costa Tavares
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| Advisor: | Elizabeth Igne Ferreira |
| Abstract | |
Chaga\'s disease is an endemic disease that aftects most part of Latin Arnerica. About 18 to 20 million people are infected by the parasite and around 50 thousand deaths are related to Chagas\' disease each year, in the 21 countries of endemic areas. The therapeutic armamentarium available against the disease is constituted by only two drugs and is insufficient, considering, also, that the drugs are not efficient in the chronic phase of the disease. As a parasitosis that only occurs in developing countries, the interest in the research for new antichagasic agents is considerably low in countries that are responsible for the introduction of new drugs in the therapeutics. So, the search for new chemotherapeutic alternatives is a task for the involved countries. In view of the situation and taking into account the high activity in in vitro tests against Trypanosoma cruzi showed by nitrofurazone hydroxymethyl derivative, an intermediary of Mannich bases reaction previously synthesized, the objective of this work was to synthesize its Mannich bases. The carriers used were aminoacids lysine and arginine and its dipeptide, lysinearginine. The compounds were synthesized using classic and alternative methods and protecting groups, currently used in peptide synthesis and others temptatively employed, as methyl and ethyl groups. Also, many experiments were performed in order to achieve the optimization of hydroxymethylnitrofurazone synthesis. The derivatives synthesized were analyzed by IR, 1H and 13C NMR, and some also by mass spectrometry. They will be submitted to in vitro tests with cell infected with T. cruzi as soon as the protecting groups are removed. Besides, tests of drug release will be performed to study their stability. We expect to obtain important information toward better comprehension of their mechanism of action and possible mutagenicity involved. (AU) | |