Design, synthesis, and biological evaluation of polyphenol derivatives as DYRK1A inhibitors. The discovery of a potentially promising treatment for Multiple Sclerosis

Abstract

Green tea and its natural components are known for their usefulness against a variety of diseases. In particular, the activity of main catechin Epigallocatechin gallate (EGCG) against Dual-specificity tyrosine-(Y)-phosphorylation Regulated Kinase-1A (DYRK1A) has been reported; here we are showing a structure-activity relationship (SAR) for EGCG against this molecular target. We have studied the influence of all four rings on the activity and the nature of its absolute geometry. This work has led to the identification of the more potent and stable trans fluoro-catechin derivative 1f (IC₅₀ = 35 nM). This molecule together with a novel delivery method showed good efficacy in vivo when tested in a validated model of multiple sclerosis (EAE).