635-21-2Relevant articles and documents
Discovery of Novel Tacrine-Pyrimidone Hybrids as Potent Dual AChE/GSK-3 Inhibitors for the Treatment of Alzheimer's Disease
Yao, Hong,Uras, Giuseppe,Zhang, Pengfei,Xu, Shengtao,Yin, Ying,Liu, Jie,Qin, Shuai,Li, Xinuo,Allen, Stephanie,Bai, Renren,Gong, Qi,Zhang, Haiyan,Zhu, Zheying,Xu, Jinyi
, p. 7483 - 7506 (2021/06/28)
Based on a multitarget strategy, a series of novel tacrine-pyrimidone hybrids were identified for the potential treatment of Alzheimer's disease (AD). Biological evaluation results demonstrated that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE) and glycogen synthase kinase 3 (GSK-3). The optimal compound 27g possessed excellent dual AChE/GSK-3 inhibition both in terms of potency and equilibrium (AChE: IC50 = 51.1 nM; GSK-3β: IC50 = 89.3 nM) and displayed significant amelioration on cognitive deficits in scopolamine-induced amnesia mice and efficient reduction against phosphorylation of tau protein on Ser-199 and Ser-396 sites in glyceraldehyde (GA)-stimulated differentiated SH-SY5Y cells. Furthermore, compound 27g exhibited eligible pharmacokinetic properties, good kinase selectivity, and moderate neuroprotection against GA-induced reduction in cell viability and neurite damage in SH-SY5Y-derived neurons. The multifunctional profiles of compound 27g suggest that it deserves further investigation as a promising lead for the prospective treatment of AD.
Monitoring intracellular pH fluctuation with an excited-state intramolecular proton transfer-based ratiometric fluorescent sensor
Feng, Bin,Zhu, Yingli,Wu, Jiaxin,Huang, Xueyan,Song, Rong,Huang, Liu,Feng, Xueping,Zeng, Wenbin
, p. 3057 - 3060 (2021/04/12)
Intracellular pH is a key parameter related to various biological and pathological processes. In this study, a ratiometric pH fluorescent sensor ABTT was developed harnessing the amino-type excited-state intramolecular proton transfer (ESIPT) process. Relying on whether the ESIPT proceeds normally or not, ABTT exhibited the yellow fluorescence in acidic media, or cyan fluorescence in basic condition. According to the variation, ABTT behaved as a promising sensor which possessed fast and reversible response to pH change without interference from the biological substances, and exported a steady ratiometric signal (I478/I546). Moreover, due to the ESIPT effect, large Stokes shift and high quantum yield were also exhibited in ABTT. Furthermore, ABTT was applied for monitoring the pH changes in living cells and visualizing the pH fluctuations under oxidative stress successfully. These results elucidated great potential of ABTT in understanding pH-dependent physiological and pathological processes.
Selenium-catalyzed intramolecular atom- And redox-economical transformation ofo-nitrotoluenes into anthranilic acids
Jiang, Xuefeng,Li, Yiming,Lin, Zhenyang,Wang, Yuhong,Yang, Tilong
supporting information, p. 2986 - 2991 (2021/05/05)
Anthranilic acids (AAs) are significant basic chemicals used in pharmaceuticals, agrochemicals, dyes, fragrances,etc. Superfluous steps are always involved in obtaining AAs. Herein, we demonstrate a straightforward strategy to transform abundanto-nitrotoluenes into biologically and pharmaceutically significant AAs without any extra reductants, oxidants and protecting groups. Various sensitive groups, such as halogens, sulfide, aldehyde, pyridines, quinolines,etc., can be tolerated in this transformation. A hundred-gram-scale operation is realized efficiently with almost quantitative selenium recycling. Further mechanistic studies and DFT calculations disclosed the proposed atom-exchange processes and the key roles of the selenium species.
