The Use of Flavylium Salts as Dynamic Inhibitor Moieties for Human Cb(5)R

Cytochrome b(5) reductase (Cb(5)R) is a flavoprotein that participates in the reduction of multiple biological redox partners. Co-localization of this protein with nitric oxide sources has been observed in neurons. In addition, the generation of superoxide anion radical by Cb(5)R has been observed. A search for specific inhibitors of Cb(5)R to understand the role of this protein in these new functions has been initiated. Previous studies have shown the ability of different flavonoids to inhibit Cb(5)R. Anthocyanins are a subgroup of flavonoids responsible for most red and blue colors found in flowers and fruits. Although usually represented by the flavylium cation form, these species are only stable at rather acidic pH values (pH ≤ 1). At higher pH values, the flavylium cation is involved in a dynamic reaction network comprising different neutral species with the potential ability to inhibit the activities of Cb(5)R. This study aims to provide insights into the molecular mechanism of interaction between flavonoids and Cb(5)R using flavylium salts as dynamic inhibitors. The outcome of this study might lead to the design of improved specific enzyme inhibitors in the future.