RESUMO
The enzyme tyrosinase is involved in the biosynthesis of melanin and the enzymatic browning of fruits and vegetables, and therefore, its inhibitors have potential to treat hyperpigmentary disorders or to function as food antibrowning agents. The use of hydrazine monohydrate as a reagent to prepare chemically engineered extracts can lead to semisynthetic compounds that contain the portion N-N, a fragment rarely found in natural products and present in some tyrosinase inhibitors. Here, we report the tyrosinase inhibition screening of a series of chemically engineered extracts that are diversified by reaction with hydrazine. LC-MS was used to evaluate the change in composition produced by the reaction. Bioguided fractionation of the most active chemically engineered extract, prepared from Matricaria recutita L., led to the discovery of a pyrazole that inhibits tyrosinase with an IC50 value of 28.20 ± 1.13 µM. This compound was produced by a one-pot double chemical transformation of its natural precursor, which includes an unexpected selective removal of one -OH group.
Assuntos
Inibidores Enzimáticos/química , Hidrazinas/química , Matricaria/química , Extratos Vegetais/química , Engenharia Química , Desenho de Fármacos , Flavonas/química , Melaninas/química , Melaninas/metabolismo , Estrutura Molecular , Monofenol Mono-Oxigenase/antagonistas & inibidores , Pirazóis/química , Relação Estrutura-AtividadeRESUMO
A set of chemically engineered extracts enriched in compounds including N-N and N-O fragments in their structures was prepared. Bromodomain binding screening and bioguided fractionation led to the identification of one oxime hit that interacts with TcBDF3 with affinity in the submicromolar range and that shows interesting antiparasitic properties against the different life cycle stages of T. cruzi.