Assuntos
Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Embolia Aérea/diagnóstico , Embolia Aérea/etiologia , Peróxido de Hidrogênio/intoxicação , Doenças Profissionais/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/terapia , Diagnóstico Diferencial , Embolia Aérea/terapia , Feminino , Tinturas para Cabelo/intoxicação , Humanos , Oxigenoterapia Hiperbárica , Fígado/diagnóstico por imagem , Fígado/patologia , Doenças Profissionais/terapia , Exposição Ocupacional , Adulto JovemRESUMO
Oncogenic Ras proteins whose activation is farnesylation by farnesyltransferase have been seen as important targets for novel anticancer drugs. Inhibitors of this enzyme have already been developed as potential anti-cancer drugs, particularly by rational design based on the structure of the CA(1)A(2)X carboxyl terminus of Ras. Synthesis of a peptidomimetics library via solid-phase synthesis using the Multipin method is described here. The most active hits on cellular assays were resynthesized and enzymatic activity was measured. Compounds A1, A5 and A7 present significant activity on the isolated enzyme (IC(50)=117, 57.3 and 28.5 nM) and their molecular docking in the active site of the enzyme provides details on key interactions with the protein.