Comparative Analysis of Novel Derivatives of Pyridoxine and Dicarboxylic Acids as Activators of Transcription Factor Nrf2.

We performed a structure-activity relationship analysis of novel maleic acid and pyridoxine derivatives, as well as epigid and morpholine fumarates, as potential inducers of Nrf2 transcription factor. A reduction in the number of hydroxyl groups in the structure of the compounds was shown to decrease their cytoprotective activity. The effectiveness of the compounds as Nrf2 activators depends not only on the presence of maleate or fumarate moieties, but also on the structure of the hydroxyaromatic fragment of the molecule. A derivative of pyridoxine and maleic acid, 3-hydroxy-4,5-bis(hydroxymethyl)-2-methylpyridin-1-ium hydromaleate, is an effective activator of Nrf2 transcription factor and exhibits cytoprotective and antioxidant activity in vitro, which suggests its further evaluation in in vivo models and its potential for novel drug development.