Design, synthesis and evaluation of 4-pyridinylthiazole-2-amines as acetylcholinesterase inhibitors / 药学学报

Alzheimer's disease (AD) is a degenerative disease of the nervous system. Compound I reported to have inhibitory activity on AChE was used as a lead compound in this study, and 4-pyridinylthiazole-2-amines were designed by optimizing compound I structure. The new compounds were synthesized from acetylpyridines through five-steps of reaction, and their inhibition activities on AChE were measured in vitro by Ellman method. The new compounds exhibited a clear inhibitory activity on AChE in vitro. The bioactivity of compound 13c was the best among them, and its IC50 value was 0.15μmol·L-1, which was better than that of rivastigmine and compound I in the control. Meanwhile, it exhibited little inhibition on butyrylcholinesterase. So the selective inhibitory activities of 4-pyridinylthiazole-2-amines to acetylcholinesterase were worth of studying furtherly.

Design, synthesis and evaluation of new L-proline derivatives as acetylcholinesterase inhibitors / 药学学报

In this paper, fourteen new L-proline derivatives were designed and synthesized, and their acetlcholinesterase (AChE) inhibitory activities were also investigated in vitro. New L-proline derivatives were prepared from substituted 2-bromo-1-acetophenones through four-step reaction; and their bioactivities as AChE inhibitors were measured by Ellman spectrophotometry. The results showed that the target compounds had a certain AChE inhibitory activity to in vitro. The bioactivity of compound 8b was the best of them, and its IC50 value was 5.45 µmol.L-1, which was better than that of rivastigmine. So the acetylcholinesterase inhibitory activities of new L-proline derivatives were worth to be further studied.

Design, synthesis and evaluation of 5-aminobenzimidazolone derivatives as acetylcholinesterase inhibitors / 药学学报

The target compounds were prepared from 5-aminobenzimidazolone by two steps reaction, and their AChE inhibitory activities were measured by Ellman method in vitro. The AChE inhibitory activity of compound 4d is the best of them, and its IC50 value is equal to 7.2 μmol·L(-1), which is better than that of rivastigmine; moreover the 4d had no inhibitory activities to BuChE. Therefore, the inhibitory activities of 5-aminobenzimidazolone derivatives to acetylcholinesterase are worth further researching.

Design, synthesis and evaluation of new L-phenylalanine derivatives as acetylcholinesterase inhibitors / 中国药学杂志

OBJECTIVE: To research the effect of new L-phenylalanine derivatives on acetylcholinesterase (AChE) activity. METHODS: New L-phenylalanine derivatives were synthesized from substituted 2-bromo-l-acetophenones by four steps reaction, and their inhibitory activities on AChE were measured by Ellman method in vitro. RESULTS: The evaluation results showed that most derivatives possessed AChE inhibitory effect and the activity of compound 8b was the most potent with an IC50 value of 8.73 × 10-6 mol · L-1, which was more potent than that of rivastigmine; moreover, compound 8b had no inhibitory activities to BuChE. CONCLUSION: The inhibitory activities of new L-phenylalanine derivatives on acetylcholinesterase are worth studying further.

Influence of Mild Hypothermia on Nervous Cell Apoptosis and Activity of Caspase - 3 after Hypoxia - Ischemia Brain Damage in Neonatal Rats / 实用儿科临床杂志

Objective To study the effects of mild hypothermia on nervous cell apoptosis and activity of Caspase - 3 after hypoxia -ischemia brain damage (HIBD) in neonatal rats. Methods Seven - day SD rats were divided into sham operation group,normothermia HIBD group (HIBD group) and mild hypothermia HIBD group(mild hypothermia group). In HIBD group,the left carotid of rats was ligated and animals were exposed to 8% oxygen for 2 h.and in mild hypothermia group,hypothermia of 31 - 32 1C lasting 8 hours was used just after HIBD. L sing methods of TUNEL and AC - DEVI) - AMC, the apoptotic cell rate and Caspase - 3 activity level were determined in sham operated group, HIBD group and mild hypothermia group separatively. Results The apoptotic cell rate and Caspase - 3 activity level were significantly lower in sham - operated group and mild hypothermia group than those in HIBD group. Conclusion One of the mechanisms of brain protection by mild hypothermia may be contributed to the decrease of neural cell apoptosis and the activity level of Caspase 3 HIBD.