1224713-90-9

Usage

Biological Activity

4'-bromo-resveratrol is a sirt1 and sirt3 inhibitor.sirtuins are protein deacetylases regulating aging processes and many physiological functions. resveratrol activates human sirt1 and inhibits sirt3, and can mimic calorie restriction effects including lifespan extension in lower organisms.

in vitro

sirtuin modulation was studied by using 4’-bromo-resveratrol in a previous study. 4’-bromo-resveratrol inhibited sirt3 with much higher potency than resveratrol, and it also inhibited rather than activated sirt1. crystal structures of human sirt3/peptide complexes of 4’ -bromo-resveratrol identified two binding sites. an internal site caused the potent inhibitory effect. 4’-bromo-resveratrol interfered with nad+ and substrate peptide binding, and it extended its bromo-phenyl group in a unrecognized site pocket. the second binding site for 4’-bromo-resveratrol was found to be located on the surface of sirt3 and connected via two helices to peptide-binding active site loops. in sirt1, this site appeared to comprise a residue that was essential for its activation by small molecules and 4’-bromo-resveratrol therefore constituted a candidate for the long-sought allosteric sirt1 activator binding site [1].

references

[1] nguyen gt, gertz m, steegborn c. crystal structures of sirt3 complexes with 4'-bromo-resveratrol reveal binding sites and inhibition mechanism. chem biol. 2013 nov 21;20(11):1375-85.

Upstream product

• 1122-91-4 4-bromo-benzaldehyde 
• 108957-75-1 diethyl 3,5-dimethoxybenzylphosphonate 
• 7311-34-4 3,5-dimethoxybenzaldehdye 
• 877-88-3 3,5-dimethoxybenzyl bromide 
• 705-76-0 3,5-dimethoxybenzyl alcohol 

Downstream Products

• 1266682-74-9 (4-[(E)-2-(3,5-dihydroxyphenyl)vinyl]phenyl)-boronic acid 

Relevant academic research and scientific papers

Stilbene Boronic Acids Form a Covalent Bond with Human Transthyretin and Inhibit Its Aggregation

Transthyretin (TTR) is a homotetrameric protein. Its dissociation into monomers leads to the formation of fibrils that underlie human amyloidogenic diseases. The binding of small molecules to the thyroxin-binding sites in TTR stabilizes the homotetramer and attenuates TTR amyloidosis. Herein, we report on boronic acid-substituted stilbenes that limit TTR amyloidosis in vitro. Assays of affinity for TTR and inhibition of its tendency to form fibrils were coupled with X-ray crystallographic analysis of nine TTR·ligand complexes. The ensuing structure-function data led to a symmetrical diboronic acid that forms a boronic ester reversibly with serine 117. This diboronic acid inhibits fibril formation by both wild-type TTR and a common disease-related variant, V30M TTR, as effectively as does tafamidis, a small-molecule drug used to treat TTR-related amyloidosis in the clinic. These findings establish a new modality for covalent inhibition of fibril formation and illuminate a path for future optimization.

Design, synthesis, and evaluation of resveratrol derivatives as Ass1-42 aggregation inhibitors, antioxidants, and neuroprotective agents

A series of novel resveratrol derivatives were designed, synthesised and evaluated as potential therapeutic agents for the treatment of Alzheimer's disease. Among these compounds, compound 7l, (E)-5-(4-(isopropylamino)styryl) benzene-1,3-diol, exhibited potent ss-amyloid aggregation inhibition activity, which was confirmed by a ThT fluorescence assay (71.65% at 20 μM) and transmission electron microscopy (TEM). Compound 7l also exhibited good antioxidant activity (4.12 Trolox equivalents in an oxygen radical absorbance capacity assay and a 37% reduction in reactive oxygen species in cells at 10 μM). The cytotoxicity analysis of compounds 7f, 7i, 7j and 7l indicated that these compounds have lower toxicities than resveratrol at 60 μM.

NOVEL STILBENE ANALOGS

The present invention relates to Stilbene derivatives of the general formula I or a pharmaceutically acceptable salt thereof have properties such as high water solubility, bioavailability and effective as carcinostatics.

USE OF HYDROXYSTILBENES FOR DYEING, READY-TO-USE COMPOSITION CONTAINING THEM AND DYEING PROCESS

The invention relates to the use of hydroxystilbenes for dyeing, to ready-to-use dye compositions comprising them, to a dyeing process using them and to a multi-compartment device containing the compositions used in the processes of the invention.