ABSTRACT
@#Ferulic acid (FA), a natural product of phenylpropanoids containing phenolic hydroxyl groups, has a wide range of pharmacological activities and some therapeutic effect on Alzheimer's disease (AD).Using FA as the raw material, the ferulic acid carbamate aniline derivatives were first synthesized by 4-step esterification reaction, splicing carbamate active functional groups, hydrolysis reaction and amide condensation.These FA derivatives were evaluated for in vitro cholinesterase inhibition activity by the Ellman method.A total of 15 novel FA derivatives were designed and synthesized, and their structures were confirmed by 1H NMR, 13C NMR and ESI-MS.Cholinesterase activity tests showed that compounds 5c, 5f, 5j, 5g, 5m possessed good acetylcholinesterase inhibition activity.Except for 5l, 5m, almost all compounds have inhibition activity on butyrylcholinesterase, which is much higher than that on acetylcholinesterase.In conclusion, compounds 5c, 5f, 5j and 5g can be used as potential anti-AD inhibitors targeting cholinesterase..
ABSTRACT
Objective To establish an effective method to rapidly detect acetylcholinesterase inhibitors from natural products, and provide support for the treatment of Alzheimer’s disease with Chinese medicine and its active ingredients. Methods The activity of restraining acetylcholinesterase of crude extracts of a variety of medicinal plants were evaluated by applying Ellman’s colorimetric, and the better activity of the extract sample solution was filtered out. The active ingredients of medicinal plants were identified and separated by the application of AS/UF-UPLC-MS. Results According to the experimental data, Corydais yanhusuo, Phellodendron chinense, Uncaria rhynchophylla, and Gynura segetum had significant restraining acetylcholinesterase activity. Rapid screening showed that 3α-dihydrocadambine, 3α-isodihydrocadambine, rhyncholphylline, isorhynchophylline, corynoxine, and isocorynoxine were active ingredients in U. rhynchophylla. Conclusion The results suggest that it is feasible to screen acetylcholinesterase inhibitors from natural organism plants. Using AS/UF-UPLC-MS methods, leading compounds for the development of new drugs for Alzheimer’s disease would be developed and provided.
ABSTRACT
Alzheimer’s disease (AD) is a primary degenerative disease of the central nervous system. The progression of Alzheimer’s disease will ultimately lead to dementia, behavioral and cognitive impairments. Increased level of the enzyme acetylcholinesterase AChE plays a key role in hydrolysis of the neurotransmitter Acetylcholine (ACh) which worsens the condition of cognitive dysfunction. Several drug of natural origin are known to possess AChE inhibition and antioxidant activity. The main objective of the present study is to evaluate AChE inhibition and antioxidant activity of the plant Ipomoea aquatica Forsk. Leaves of Ipomoea aquatica Forsk was extracted with Chloroform, n-Hexane, Ethanol and mixture of Ethanol: water (6:4) (hydro-alcoholic extract) using soxhlet extraction. All the four extracts were examined for In-vitro anti-cholinesterase by Ellman’s method and antioxidant activity by DPPH and Hydrogen peroxide radical scavenging assay. Results obtained from the study clearly demonstrates that all four extract has shown promising acetylcholinesterase inhibition activity in hydro alcoholic extract reveals the best inhibition potential with IC50 49.03 μg /ml. Similarly all the extracts projects significant antioxidant activity in DPPH assay with IC50 value ranging from 19.64 to 88.63 μg /ml and in Hydrogen peroxide assay with IC50 value ranging from 56.79 to 137.3 μg /ml.