879924-00-2Relevant academic research and scientific papers
Discovery of the first-in-class dual PPARδ/γ partial agonist for the treatment of metabolic syndrome
Li, Zheng,Ren, Qiang,Zhou, Zongtao,Cai, Zongyu,Wang, Bin,Han, Jing,Zhang, Luyong
, (2021/08/30)
The peroxisome proliferator-activated receptors (PPARs) exert vital function in the regulation of energy metabolism, which were considered as promising targets of metabolic syndrome. Until now, PPARδ/γ dual agonist is rarely reported, and thereby the pharmacologic action of PPARδ/γ dual agonist is still unclear. In this study, we identified a dual PPARδ/γ partial agonist 6 (ZLY06) based on the cyclization strategy of PPARα/δ dual agonist GFT505. ZLY06 revealed excellent pharmacokinetic profiles suitable for oral medication. Moreover, ZLY06 markedly improved glucolipid metabolism without weight gain, and alleviated fatty liver by promoting the β-oxidation of fatty acid and inhibiting hepatic lipogenesis. In contrast, weight gain and hepatic steatosis were observed in Rosiglitazone, a widely used PPARγ full agonist. All of these results indicated that ZLY06 exhibits potential benefits on metabolic syndrome, while no adverse effects related to PPARγ full agonist.
Synthesis of some new 3-coumaranone and coumarin derivatives as dual inhibitors of acetyl- and butyrylcholinesterase
Alipour, Masoumeh,Khoobi, Mehdi,Nadri, Hamid,Sakhteman, Amirhossein,Moradi, Alireza,Ghandi, Mehdi,Foroumadi, Alireza,Shafiee, Abbas
, p. 577 - 587 (2013/09/02)
A novel series of coumarin and 3-coumaranone derivatives encompassing the phenacyl pyridinium moiety were synthesized and evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity using Ellman's method. All compounds presented inhibitory activity against both AChE and BuChE in the micromolar range. The molecular docking simulations revealed that all compounds were dual binding site inhibitors of AChE. A kinetic study was performed and the mechanism of enzyme inhibition was proved to be of mixed type. All compounds were tested for their antioxidant activity and no significant activity was observed.
Design, synthesis and anticholinesterase activity of a novel series of 1-benzyl-4-((6-alkoxy-3-oxobenzofuran-2(3H)-ylidene) methyl) pyridinium derivatives
Nadri, Hamid,Pirali-Hamedani, Morteza,Shekarchi, Maryam,Abdollahi, Mohammad,Sheibani, Vahid,Amanlou, Massoud,Shafiee, Abbas,Foroumadi, Alireza
experimental part, p. 6360 - 6366 (2010/10/01)
A novel series of benzofuranone-ylidene-methyl benzylpyridinium derivatives (6a-u) were synthesized as acetylcholinesterase inhibitors. The anticholinesterase activity of synthesized compounds was measured using colorimetric Ellman's method. It was revealed that some synthesized compounds exhibited high anticholinesterase activity, among them compound 6b was the most active compound (IC50 = 10 ± 6.87 nM).
