| Alzheimer’s disease(AD) is acknowledged as a progressive neurodegenerative disorder, associated with loss of memory, cognitive decline, and behavioral disability, ultimately leading to death. Now the country’s population is aging fast. It is estimated that by 2050, one new case of AD is expected to develop every 33 seconds, which will bring heavy burden to society and family. So far, medical workers have not found a drug can radically cure AD. Acetylcholinesterase(ACh E) inhibitors, which can significantly relieve clinical symptoms, become the first choice to treat AD at present. However, the existing ACh E inhibitors are still unable to meet the clinical needs. Now researchers are still committed to finding more effective and less toxic ACh E inhibitors.In this paper, substituted phenylhydrazine and ethyl cyanoacetate were selected as starting materials, and a series of novel 5-amino-pyrazol-3-one derivatives were designed and prepared. Furthermore all the synthesized compounds were confirmed by 1H-NMR, MS and IR spectra.In order to study the biological activity of these compounds, Ellman method was adopted to examine their ACh E inhibitory activity in vitro. The results showed that the synthesized compounds had a certain inhibitory activity to ACh E. Among them, the bioactivity of 7c was the best, and IC50 of 7c was 3.36 μM, better than that of rivastigmine and less than donepezil.Moreover, the kinetic study of compound 7c was carried out to study the acting mechanism of the compound on acetylcholinesterase, and the Line weaver-Burk plots showed there is a mixed type of competitive inhibition. |
PDF Full Text Request