Exploring the mechanism of flavonoid amination and its potential biological implications from an in-vitro and in-vivo perspective.

Abstract

The discovery of flavonoid amination metabolism has raised research interest in this new biotransformation mechanism. In vitro studies have revealed that flavonoids with pyrogallol structures readily react with N-nucleophilic ammonia, where amination occurs at intermediate -OH position, such as the B ring C4'-OH of epigallocatechin gallate and myricetin, A ring C6-OH of baicalein. Flavonoids are also covalently bound with amino acid residue by Schiff base, Michael addition or Strecker degradation, which are further rearranged to generate -NH₂ substituted products. Amination transformation is mainly related to the interaction of flavonoids with amino acids, with the pathway occurring mainly in the liver and gut, where the intestinal microbiota promotes the formation of aminated metabolites. The introduction of -NH₂ not only preserves the basic activity of flavonoids, but it also has biological significance in ammonia detoxification. Furthermore, flavonoids serve as an anti-amyloidosis agent by amination, preventing the related diseases. Amination modification alters flavonoid polarity and spatial conformation, which facilitates their target interaction with enzymes (topoisomerase II), molecular docking confirming that they bind to amino acid residues in a pattern similar to that of Adriamycin. It is worth further exploring the biological effects induced by flavonoid amination, which may be a promising modification strategy.