Anti-oxidant activity of 1-(1H-imidazo[4,5-c]pyridin-4-yl)ethenone, a Maillard reaction product derived from fructose and histidine.

Abstract

The Maillard reaction involves the interaction of various amino acids and reducing sugars, resulting in food browning. It often produces appealing aromas and flavors. The complexities of the reaction are such that it can be challenging to identify the often numerous and frequently volatile products formed by it. In the present study, we sought to identify and evaluate an unusual product with anti-oxidant activity arising from a fructose-histidine Maillard reaction model. The anti-oxidant profile of this product was assessed by computational means. The fructose-histidine Maillard reaction products (FH-MRPs) were generated by heating a 2:1 mixture of the sugar and the amino acid at 140 °C for 2 h. Chromatographically separable fractions, labelled DM-1 to DM-8, were obtained using silica gel as the stationary phase and dichloromethane/methanol (DCM/MeOH) mixtures as the mobile one. Fraction DM-5 exhibited the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, and further bio-assay guided fractionation led to isolation and identification of 1-(1H-imidazo[4,5-c]pyridin-4-yl)ethenone (IMPE) as the active principal, the structure of which was established by nuclear magnetic resonance (NMR) spectroscopic and mass spectral techniques. A mechanism for the formation of IMPE from its precursors is proposed. Density functional theory (DFT) calculations suggest this novel heterocyclic compound exerts its anti-oxidant effects by interacting with DPPH and 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals. Essentially, IMPE was non-toxic below 300 ug mL-1, showing a concentration-dependent free radical clearance capacity and reducing power within the 100-1000 μg mL-1 range, and moreover, exhibiting significant Fe2+ chelating abilities wihin the 50-200 μg mL-1 range. This study identified the unique FH-MRP, IMPE, and found that it acts as food antioxidant through the chelation of metal ions. © 2024 Society of Chemical Industry.