Estudio de la relación estructura-actividad de tiazolilhidrazonas derivadas de 1-indanonas con acción anti-Trypanosoma cruzi

This thesis work includes the exhaustive study of the structure-activity relationship and action mechanism through the use of different computational methodologies of thiazolylhydrazones (TZHs) derived from 1-indanones. These compounds were previously synthesized by the research group and showed ver...

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Autor principal: Noguera, Guido Julián
Otros Autores: Fabian, Lucas
Formato: Tesis doctoral acceptedVersion
Lenguaje:Español
Publicado: Facultad de Farmacia y Bioquímica 2017
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Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_3149
http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_3149.dir/3149.PDF
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Sumario:This thesis work includes the exhaustive study of the structure-activity relationship and action mechanism through the use of different computational methodologies of thiazolylhydrazones (TZHs) derived from 1-indanones. These compounds were previously synthesized by the research group and showed very good activity values against the different forms of Trypanosoma cruzi (T. cruzi), etiologic agent of Chagas disease. QSAR, shape matching, docking and molecular dynamics studies allowed to establish the necessary structural requirements for anti-T. cruzi activity and to determine that the TZHs interfere in ergosterol biosynthesis by inhibiting the enzyme squalene epoxidase (SE). The different theoretical models generated in this thesis work will allow the rational design of new inhibitors of the T. cruzi SE that present the established characteristics to be able to become potential candidates for drugs for the treatment of this disease.