139311-84-5Relevant articles and documents
Design, synthesis, and biological evaluation of a novel dual peroxisome proliferator-activated receptor alpha/delta agonist for the treatment of diabetic kidney disease through anti-inflammatory mechanisms
Liu, Kai,Zhao, Xing,Qi, Xue,Hou, Dong-Liang,Li, Hao-Bin,Gu, Yu-Hao,Xu, Qing-Long
, (2021/04/02)
Diabetic kidney disease (DKD) is a major feature of the final stage of nearly all cause types of diabetes mellitus (DM). To date, few safe and effective drugs are available to treat. Peroxisome proliferator-activated receptors (PPARs), comprised of three members: PPAR-α, PPAR-δ and PPAR-γ, play a protective role in the DKD through glycemic control and lipid metabolism, whereas systemic activation of PPAR-γ causes serious side-effects in clinical trials. GFT505 is a dual PPAR-α/δ agonist, and the selectivity against PPAR-γ is still to be improved. Sulfuretin has been shown to suppress the expression of PPAR-γ and improve the pathogenesis of diabetic complications. In this study, by hybridizing the carboxylic acid of GFT505 and the parent nucleus of sulfuretin, we pioneeringly designed and synthetized a series of novel dual PPAR-α/δ agonists, expecting to provide a better benefit/risk ratio for PPARs. Of all the synthesized compounds, compound 12 was identified with highly activity on PPAR-α/δ and higher selectivity against PPAR-γ than that of GFT505 (EC50: hPPAR-α: 0.26 μM vs.0.76 μM; hPPAR-δ: 0.50 μM vs.0.73 μM; hPPAR-γ: 4.22 μM vs.2.79 μM). The molecular docking studies also depicted good binding affinity of compound 12 for PPAR-α and PPAR-δ compared to GFT505. Furthermore, compound 12 exhibited an evidently renoprotective effect on the DKD through inhibiting inflammatory process, which might at least partly via JNK/NF-κB pathways in vivo and in vitro. Overall, compound 12 hold therapeutic promise for DKD.
The first synthesis of peracetyl glycosyl aurone derivatives and aurone glucosides
Kafle, Arjun,Bhattarai, Shrijana,Handy, Scott T.
supporting information, (2020/09/09)
Aurones, a sub-class of the flavonoids with proven therapeutic importance, also exist in variously glycosylated forms. Although a large number of glycosylated aurone derivatives have been isolated from plant sources, no syntheses have been reported yet. Inspired from this gap, here we report the first synthesis of peracetylated glycosyl derivatives of synthetic aurones. The direct O-glycosylation was achieved by reacting 6-hydroxy aurones with 2, 3, 4, 6-tetra-O-acetyl-α-D glucopyranosyl bromide in the presence of a phase transfer catalyst tetrabutylammonium bromide (TBAB). The successful synthesis of aurone glycosides (33 examples) in 60–92% yield will benefit the synthesis of combinatorial libraries of glycosylated aurones for their biological study and comparison with non-glycosylated aurones.
Synthesis and Biological Activities of 6-Hydroxyaurone Derivatives
Bao, Yong-Tuan,Zhang, Min,Li, Ting,Xiao, Hui-Feng,Zhao, Ting,Xu, Xiao-Hua,Yang, Liu-Qing
, p. 637 - 642 (2016/04/19)
A series of 6-hydroxyaurone derivatives were synthesized in satisfactory yields and characterized by IR, 1H NMR, 13C NMR, and HRMS or elemental analysis. The structure of compound 3e was further confirmed by X-ray crystal analysis. B
Synthesis of 2-(p-Chlorobenzyl)-3-aryl-6-methoxybenzofurans as Selective Ligands for Antiestrogen-Binding Sites. Effects on Cell Proliferation and Choresterol Synthesis
Teo, Chin Chin,Kon, Oi Lian,Sim, Keng Yeow,Ng, Siu Choon
, p. 1330 - 1339 (2007/10/02)
A series of nonsteroidal compounds, 2-(p-chlorobenzyl)-3-aryl-6-methoxybenzofurans derived from the 2-(p-chlorobenzyl)-6-methoxy-3(2H)-benzofuranones has been synthesized.The key steps in the synthesis were reactions of 2-(p-chlorobenzyl)-6-methoxy-3(2H)-benzofuranones with the arylorganometallic reagents followed by dehydration of the resulting carbinols.The benzofurans are ligands for antiestrogen-binding sites (AEBS) and display no significant interaction with the estrogen receptor (ER).All bind to AEBS with equivalent or greater affinity than tamoxifen.These compounds decrease thymidine incorporation in AEBS-containing EL4 lymphoid cells and MCF7 breast cancer cells in a concentration-dependent manner between 10-8 and 10-6 M and are generally more inhibitory than tamoxifen.In contrast, they have no effect on thymidine incorporation by an AEBS-deficient variant of the MCF7 cell line, RTx6.The present findings of (1) selective and high affinity binding of the benzofurans to AEBS, (2) their concentration-dependent inhibition of thymidine incorporation in AEBS-containing cells, and (3) their lack of antiproliferative effect in an AEBS-deficient cell line suggest a functional role for AEBS in mediating the antigrowth effect of these compounds.Two of the more active benzofuran compounds also significantly inhibited de novo cholesterol biosynthesis in EL4 cells which lack ER.This effect could be obtained after 5 h of treatment and preceded significant loss of cell viability.This is the first demonstration that selective ligands of AEBS (other than the known nonsteroidal antiestrogens) interfere with cholesterol biosynthesis - an action that may contribute to their antigrowth effect.
