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| Author(s): |
Kesley Moraes Godinho de Oliveira
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Química |
| Defense date: | 2009-06-26 |
| Examining board members: |
Yuji Takahata;
Anderson Coser Gaudio;
Antonia Tavares do Amaral;
Pedro Antonio Muniz Vazquez;
Munir Salomão Skaf
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| Advisor: | Yuji Takahata; Rogério Custodio |
| Abstract | |
The object of study of this thesis is the most severe and lethal form of leishmaniasis: visceral leishmaniasis, LV, whose main etiological agent is the species Leishmania donovani. The goal of this work is the development of Quantitative Structure-Activity Relationship models for two series of compounds presenting antileishmanial activity against amastigotes of Leishmania donovani. The first series includes twenty-one analogues of pyrazolo-pyrimidine nucleosides and the second series comprises eight antifungals. To ensure the robustness of the models, in addition to the compounds that make up their series, molecules with known activity against LV were selected to compose a testset and evaluate the predictive power of their models. For the series of nucleosides logistic regression models and tree classification were developed. In both approaches, the Mor26v and GAP(HOMO, HOMO-1) descriptors were relevant to explain the leishmanicidal activity of these compounds. The logistic regression model reached 90.5% for classification accuracy to the workingset and 58% for testset after analysis of the domain of applicability of the model. The classification tree model reached 95% for classification accuracy of the workingset and 86% for the testset. A multiple linear regression model was applied to the series of antifungal agents. The electron energy and polar surface area were important for the leishmanicidal activity of this series. The predicted values showed 98% of correlation with the experimental values. The values found for the testset are also in agreement with the literature. Finally, new compounds were proposed for synthesis and evaluation of leishmanicidal activity. (AU) | |