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| Author(s): |
Roberto Parise Filho
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) |
| Defense date: | 2003-12-18 |
| Examining board members: |
Maria Amelia Barata da Silveira;
Magali Benjamin de Araujo;
Chung Man Chin;
Liliana Marzorati;
Seizi Oga
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| Advisor: | Maria Amelia Barata da Silveira |
| Abstract | |
Schistosomiasis, a tropical disease that affects humans for millions of years, is among the parasitic great incidence illness in subdeveloped countries. Even after all advances gotten in the treatment and prevention, the disease still has significative numbers of prevalence and morbity. The disease is directly associated with low acquisitive power, the Jack of information and bad sanitary and habitat conditions. The trematodes of Schistosoma gender are considered the disease causing agents, and the most important species that affect humans are S. mansoni, S. mekongi e S. japonicum, S. haematobium e S. intercalatum: others species affect human less frequently. Oxamniquine is an schistosomicide agent wide/y used in brazilian therapeutics against S. mansoni, due to low cost and good efficacy. Although the drug is relatively we/1 tolerated, some adverse effects in the central nervous system, as convulsions and alucinations have been described. The latentiation method was proposed with the aim to achieve polymeric prodrugs, allowing prolonged action and reduction of adverse effects. Polyacryloil and polymethacryloil derivatives were choosed to be the carriers and aminoacids (aminocaproic acid, gama-aminobutyric acid and glycine) were used as spacer groups. The acrylic and methacrylic prodrugs were obtained and a complete characterization was performed. The copolymer, poly (methacrylic-co-oxamniquine methacrylate) acid, was characterized by infrared spectrometry, thermal analysis and X-ray difratometry. The polymer and copolymer of the acrylic prodrug were not obtained. Although the oxamniquine prodrugs were not obtained yet, the acrylamidics and methacrylamidc derivativas of aminoacids were achieved with high purity degree. The molecular modeling solved some problems related to the oxamniquine\'s spacial structure and the obtention of its derivatives. An oxamniquine\'s cyclic derivative was achived by an unpublished reaction and still remains under research. The substitution degree of the copolymer was determined to determine the efective dose. The biological activity of the acrylic, methacrylic prodrugs and copolymer was evaluated by the quantitative oogram method and mesenteric blood vessels perfusion. Results show activity for the prodrugs, but not for the polymeric prodrug. (AU) | |