896121-43-0Relevant academic research and scientific papers
Design, synthesis, and biological evaluation of polyphenol derivatives as DYRK1A inhibitors. The discovery of a potentially promising treatment for Multiple Sclerosis
Araldi, Gian Luca,Hwang, Yu-Wen
, (2022/03/27)
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).
A structure-activity study for the inhibition of metalloproteinase-9 activity and gene expression by analogues of gallocatechin-3-gallate
Dell'Agli,Bellosta,Rizzi,Galli,Canavesi,Rota,Parente,Bosisio,Romeo
, p. 2896 - 2903 (2007/10/03)
Catechins are able to modulate the gelatinolytic activity of matrix metalloproteinase-9 (MMP-9) by reducing its release from macrophages. Gallocatechins decrease MMP-9 secretion by lowering MMP-9 promoter activity and mRNA levels. The effect appears to be dependent on some structural and stereochemical requirements. In this study, the relationship between chemical structure and activity was studied by testing the effect of analogues of (±)-gallocatechin-3-gallate (±)-GCG, selectively deprived of hydroxyl groups, on MMP-9 activity, transcription, and secretion. Our results indicate that (±)-GCG and (±)-catechin-3-gallate are characterized by a substitution pattern compatible with direct inhibition of MMP-9 activity. Conversely, when transcription was the target, (±)-trans-3-flavanol-3- benzoate, lacking all the hydroxyl groups, was the most effective both in lowering MMP-9 promoter activity and consequently protein secretion, and in inhibiting nuclear-factor-κB-driven transcription. Our results suggest that the structural requirements for enzyme inhibition are different from those necessary for targeting gene expression. Birkhaeuser Verlag, 2005.
