Facultad de Ciencias Bioquímicas y Farmacéuticas , Universidad Nacional de Rosario-CONICET , Suipacha 531 , 2000 , Rosario , Argentina.
ACS Comb Sci. 2019 Sep 9;21(9):622-627. doi: 10.1021/acscombsci.9b00064. Epub 2019 Aug 14.
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 L., led to the discovery of a pyrazole that inhibits tyrosinase with an IC 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.
酪氨酸酶参与黑色素的生物合成和水果蔬菜的酶促褐变，因此，其抑制剂具有治疗色素沉着紊乱或作为食品防褐变剂的潜力。使用水合肼作为试剂来制备化学工程提取物可以得到含有 N-N 部分的半合成化合物，该部分在天然产物中很少见，但存在于一些酪氨酸酶抑制剂中。在这里，我们报告了一系列通过与水合肼反应进行化学工程化的提取物的酪氨酸酶抑制筛选。LC-MS 用于评估反应产生的组成变化。从 L. 制备的最活跃的化学工程提取物的生物导向分段分离导致发现了一种吡唑，其对酪氨酸酶的抑制作用的 IC 值为 28.20 ± 1.13 μM。该化合物由其天然前体的一锅双化学转化产生，其中包括一个意想不到的选择性去除一个 -OH 基团。
