Aplicación biotecnológica de los organismos C. elegans y D. reriopara el descubrimiento de los nuevos fármacos : utilización de mutantes de la vía de MAPK como modelos de cáncer de colon
New strategies for developing K-Ras inhibitors are needed. The aim of this work is to use a novel and integrative protocol in order to develop molecules that can bind to Ras and inhibit it proliferative activity.\nFirst of all, a docking in silico strategy was used and the interaction of a virtual...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2018
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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_3158 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_3158.dir/3158.PDF |
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| Sumario: | New strategies for developing K-Ras inhibitors are needed. The aim of this work is to use a novel and integrative protocol in order to develop molecules that can bind to Ras and inhibit it proliferative activity.\nFirst of all, a docking in silico strategy was used and the interaction of a virtual library of drug-like molecules was explored. Having identified the best candidates, those were purchased to commercial vendors and their activity was tested in vivo in the model C. elegans. In addition, the fish D. rerio was used for evaluating their toxicity.\nUsing these two approaches in an iterative way, two molecules were recognized. The process was continued by testing them on cell cultures in vitro and in rodent models in vivo: Those molecules that showed better activity on cell cultures were chemically modified looking for an improved activity profile. Once a candidate was observed, it was synthetized and it activity and toxicity was measured in an in vivo model for liver metastases, presenting favorable results, reducing the amount of mice showing metastases and metastases spots on them. \n |
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