RESUMO
Glutathione reductase (GR) is a crucial antioxidant enzyme which is responsible for the maintenance of antioxidant GSH molecule. Antimalarial effects of some chemical molecules are attributed to their inhibition of GR, thus inhibitors of this enzyme are expected to be promising candidates for the treatment of malaria. In this work, GR inhibitory properties of N-Methylpyrrole derivatives are reported. It was found that all compounds have better inhibitory activity than the strong GR inhibitor N,N-bis(2-chloroethyl)-N-nitrosourea, especially three molecules, 8 m, 8 n, and 8 q, were determined to be the most powerful among them. Findings of our study indicates that these Schiff base derivatives are strong GR inhibitors which can be used as leads for designation of novel antimalarial candidates.
Assuntos
Antimaláricos/farmacologia , Inibidores Enzimáticos/farmacologia , Glutationa Redutase/antagonistas & inibidores , Malária/tratamento farmacológico , Pirróis/farmacologia , Antimaláricos/síntese química , Antimaláricos/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Glutationa Redutase/metabolismo , Malária/metabolismo , Estrutura Molecular , Pirróis/síntese química , Pirróis/química , Relação Estrutura-AtividadeRESUMO
This study represents an expansion of the application of catalysis in air through conventional coupling and free radical processes. A reactive free aryl radical intermediate was generated via the oxidation of an activated Ar-NH-NH2 bond by air as a simple and readily available oxidant. For this purpose, the usability of phenylhydrazine and phenylhydrazine hydrochloride salt reagents for the direct arylation of pyrrole with aryl radicals was investigated. The facile coupling of N-methylpyrrole with aryl radicals was easily applied for the convenient direct synthesis of C-2 arylated pyrroles without a transition-metal catalyst.
