3232-36-8Relevant articles and documents
Modulation of estrogen-related receptors subtype selectivity: Conversion of an ERRβ/γ selective agonist to ERRα/β/γ pan agonists
Avdagic, Amer,Billon, Cyrielle,Burris, Sheryl L.,Burris, Thomas P.,Elagawany, Mohamed,Elgendy, Bahaa,Goher, Shaimaa S.,Hegazy, Lamees,Sanders, Ryan,Shahien, Mohamed,Sitaula, Sadichha
, (2020/07/21)
Estrogen Related Receptors (ERRs) are key regulators of energy homeostasis and play important role in the etiology of metabolic disorders, skeletal muscle related disorders, and neurodegenerative diseases. Among the three ERR isoforms, ERRα emerged as a potential drug target for metabolic and neurodegenerative diseases. Although ERRβ/γ selective agonist chemical tools have been identified, there are no chemical tools that effectively target ERRα agonism. We successfully engineered high affinity ERRα agonism into a chemical scaffold that displays selective ERRβ/γ agonist activity (GSK4716), providing novel ERRα/β/γ pan agonists that can be used as tools to probe the physiological roles of these nuclear receptors. We identified the structural requirements to enhance selectivity toward ERRα. Molecular modeling shows that our novel modulators have favorable binding modes in the LBP of ERRα and can induce conformational changes where Phe328 that originally occupies the pocket is dislocated to accommodate the ligands in a rather small cavity. The best agonists up-regulated the expression of target genes PGC-1α and PGC-1β, which are necessary to achieve maximal mitochondrial biogenesis. Moreover, they increased the mRNA levels of PDK4, which play an important role in energy homeostasis.
Multiple Hydrogen Bonds Promoted ESIPT and AIE-active Chiral Salicylaldehyde Hydrazide
Wang, Man,Cheng, Caiqi,Song, Jintong,Wang, Jun,Zhou, Xiangge,Xiang, Haifeng,Liu, Jin
supporting information, p. 698 - 707 (2018/06/06)
The simpler, the better! A series of simple and highly fluorescent salicylaldehyde hydrazide molecules (41 samples) have been designed and prepared. Even though these soft materials contain a very small π-conjugated system, they can go through multiple intramolecular and intermolecular hydrogen bonds promoted excited-state intramolecular proton-transfer (ESIPT) to display strong blue, green, yellow, and orange aggregation-induced emission (AIE) with large Stokes shifts (up to 184 nm) and high fluorescence quantum yields (Ф up to 0.20). Unusual mechanochromic fluorescence enhancements are also found in some solid samples. Through coordination, hydrogen and halogen bonds, these flexible molecules can be used as Mg2+ (Ф up to 0.46) probes, universal anion (Ф up to 0.14) and unprotected amino acids (Ф up to 0.16) probes, and chiral diamine (enantiomeric selectivity and Ф up to 0.36 and 0.062, respectively) receptors. Combining their advantages of AIE and biocompatibility, these low cytotoxic dyes have potential application in living cell imaging. Furthermore, the effects of different functional groups on the molecule arrangement, ESIPT, AIE, probe, and chiral recognition properties are also examined, which provide a simple and bright paradigm for the design of multiple-stimuli-responsive smart materials.
Synthesis and biological activity of hydrazones of o- and p-hydroxybenzoic acids. Spatial structure of 5-Bromo-2-hydroxybenzylidene-4-hydroxybenzohydrazide
Nurkenov,Satpaeva, Zh. B.,Schepetkin,Khlebnikov,Turdybekov,Seilkhanov,Fazylov
, p. 2299 - 2306 (2017/11/24)
A series of hydrazones based on hydrazides of o- and p-hydroxybenzoic acids have been prepared. N-(5-Bromo-2-hydroxybenzylidene)-4-hydroxybenzohydrazide has been studied by X-ray diffraction analysis; its molecule forms hydrogen bond with a solvating ethanol molecule. Biological activity of the synthesized hydrazones towards cathepsin Е and(or) elastase of human neutrophils has been determined.
