DISEÑO IN SILICO DE IMIDAZOLES FUNCIONALIZADOS CON AMINOÁCIDOS COMO INHIBIDORES DE LAS PROTEÍNAS NS3 Y NS5 DEL VIRUS DEL DENGUE
Palavras-chave:
diseño de fármacos; acoplamiento molecular; ADME+T; DFT; virus del dengue; imidazoles funcionalizados con aminoácidos.Resumo
Se diseñaron 252 imidazoles funcionalizados con aminoácidos para evaluar sus
posibilidades como inhibidores, mediante técnicas computacionales. Un análisis de los
perfiles ADME+T indica, que los compuestos derivados de los aminoácidos polares Ser y
Thr, son los más favorables como candidatos a fármacos. De estos compuestos, cuatro (SerA22, Thr-A22, Ser-A35 y Thr-A35) resaltan como candidatos a inhibidores de las proteínas
NS3 en su dominio helicasa y NS5 en su dominio metiltransferasa. Para los dominios NS2BNS3Pro y NS5RdRp los resultados no son alentadores. Un análisis de las densidades
electrónicas de estos cuatro compuestos mediante DFT, arrojó la similitud con inhibidores
de referencia en cuanto a orbitales de frontera, reactividad y superficies de potencial
electrostático, lo cual explica la fortaleza de la unión de estos compuestos con las proteínas
virales.
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