1481-83-0Relevant academic research and scientific papers
Towards the discovery of drug-like epigallocatechin gallate analogs as Hsp90 inhibitors
Bhat, Rohit,Adam, Amna T.,Lee, Jungeun Jasmine,Gasiewicz, Thomas A.,Henry, Ellen C.,Rotella, David P.
, p. 2263 - 2266 (2014/05/20)
(-)-Epigallocatechin gallate (EGCG) is the major flavonoid of green tea and has been widely explored for a range of biological activities including anti-infective, anti-inflammatory, anti-cancer, and neuroprotection. Existing structure-activity data for EGCG has been largely limited to exploration of simple ethers and hydroxyl deletion. EGCG has poor drug-like properties because of multiple phenolic hydroxyl moieties and a metabolically labile ester. This work reports a substantial expansion of structure-activity understanding by exploring a range of semi-synthetic and synthetic derivatives with ester replacements and variously substituted aromatic and alicyclic groups containing more drug-like substituents. Structure-activity relationships for these molecules were obtained for Hsp90 inhibition. The results indicate that amide and sulfonamide linkers are suitable ester replacements. Hydroxylated aromatic rings and the cis-stereochemistry in EGCG are not essential for Hsp90 inhibition. Selected analogs in this series are more potent than EGCG in a luciferase refolding assay for Hsp90 activity.
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.
Reactions of Flav-2-enes and Flav-2-en-4-ones (Flavones)
Bird, T. Geoffrey C.,Brown, Ben R.,Stuart, Ian A.,Tyrrell, William R.
, p. 1831 - 1846 (2007/10/02)
Flav-2-enes, flavones, and 3-alkyl ethers of flavonols add alcohols and carboxylic acids in the presence of N-bromosuccinimide to give 2-alkoxy- and 2-acyloxy-3-bromoflavans which provide routes to cis-3-bromoflavans by reduction and to 3,4-diols by elimination and reaction with osmium tetraoxide.The 2-acyloxyflavans react with alcohols yielding 2-alkoxyflavans.Flavonols react with N-bromosuccinimide and alcohols to give bromine-free hemiacetals, the known 2,3-dialkoxy-3-hydroxyflavanones.
