13351-10-5Relevant articles and documents
COMPOSITIONS AND METHODS OF TREATING UPS-ASSOCIATED DISEASES
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, (2022/01/24)
The present invention relates to methods for treating a disease characterized by aberrations in the ubiquitin/proteasome system (UPS).
Chromone derivatives bearing pyridinium moiety as multi-target-directed ligands against Alzheimer's disease
Abdpour, Shahin,Jalili-Baleh, Leili,Nadri, Hamid,Forootanfar, Hamid,Bukhari, Syed Nasir Abbas,Ramazani, Ali,Ebrahimi, Seyed Esmaeil Sadat,Foroumadi, Alireza,Khoobi, Mehdi
, (2021/03/14)
A new serise of 7-hydroxy-chromone derivatives bearing pyridine moiety were synthesized, and evaluated as multifunctional agents against Alzheimer's disease (AD). Most of the compounds were good AChE inhibitors (IC50 = 9.8–0.71 μM) and showed remarkable BuChE inhibition activity (IC50 = 1.9–0.006 μM) compared with donepezil as the standard drug (IC50 = 0.023 and 3.4 μM). Compounds 14 and 10 showed the best inhibitory activity toward AChE (IC50 = 0.71 μM) and BuChE (IC50 = 0.006 μM), respectively. The ligand–protein docking simulations and kinetic studies revealed that compound 14 and 10 could bind effectively to the peripheral anionic binding site (PAS) of the AChE and BuChE through mixed-type inhibition. In addition, the most potent compounds showed acceptable neuroprotective activity on H2O2- and Aβ-induced.neurotoxicity in PC12 cells, more than standard drugs. The compounds could block effectively self- and AChE-induced Aβ aggregation. All the results suggest that compounds 14 and 10 could be considered as promising multi-target-directed ligands against AD.
Synthesis and biological evaluation of isoliquiritigenin derivatives as a neuroprotective agent against glutamate mediated neurotoxicity in HT22 cells
Selvaraj, Baskar,Kim, Dae Won,Huh, Gyuwon,Lee, Heesu,Kang, Kyungsu,Lee, Jae Wook
, (2020/03/05)
Glutamate-induced neurotoxicity is characterized by cellular Ca2+ uptake, which is upstream of reactive oxygen species (ROS)-induced apoptosis signaling and MAPKs activation. In the present study, we synthesized isoliquiritigenin analogs with electron-donating and electron-withdrawing functional groups. These analogs were evaluated for neuroprotective effect against glutamate-induced neurotoxicity in HT22 cells. Among these analogs, compound BS11 was selected as a potent neuroprotective agent. Cellular Ca2+ concentration, ROS level, MAPKs activation and AIF translocation to the nucleus were increased upon treatment with 5 mM glutamate. In contrast, we identified that compound BS11 reduced the cellular Ca2+ concentration and ROS level upon glutamate exposure. Western blot analysis showed that MAPK activation was decreased by treatment with compound BS11. We further identified that cotreatment of compound BS11 and glutamate inhibited translocation of AIF to the nucleus.