Liu, Yulin published the artcileNovel inhibitors of AChE and Aβ aggregation with neuroprotective properties as lead compounds for the treatment of Alzheimer’s disease, Category: ethers-buliding-blocks, the publication is European Journal of Medicinal Chemistry (2022), 114305, database is CAplus and MEDLINE.
A series of sulfone analogs of donepezil I (R1 = H, F; R2 = H, 4-F, 3-Cl, etc.) were designed and synthesized as novel acetylcholinesterase (AChE) inhibitors with the potent inhibiting Aβ aggregation and providing neuroprotective effects as potential modalities for Alzheimer’s disease (AD). Most of the target compounds displayed effective inhibition of AChE, especially compound II which displayed powerful inhibitory activity (IC50 = 2.4 nM). Kinetic and docking studies indicated that compound II was a mixed-type inhibitor. Furthermore, in glyceraldehyde (GA)-exposed SH-SY5Y differentiated neuronal cells, compound II could potently inhibit AChE, reduce tau phosphorylation at S396 residue, provide neuroprotection by rescuing neuronal morphol. and increasing cell viability. It was also found to reduce amyloid aggregation in the presence of AChE. In addition, compound II showed evident protections from mitochondrial membrane dysfunction and oxidative stress in okadaic acid-induced pharmacol. models. Moreover, compound II exhibited more effective treatment prospects in vivo than donepezil, including a moderate blood-brain barrier permeability, a more potent AChE inhibitory activity and behavioral improvement in scopolamine-induced cognition-impaired mice model at a much lower dose. Collectively, compound II is a promising lead compound for further investigation to discovery and development of new anti-AD agents.
European Journal of Medicinal Chemistry published new progress about 91-16-7. 91-16-7 belongs to ethers-buliding-blocks, auxiliary class Benzene,Ether,Inhibitor,Inhibitor,Inhibitor, name is 1,2-Dimethoxybenzene, and the molecular formula is C8H10O2, Category: ethers-buliding-blocks.
Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem