AI Article Synopsis
- The study synthesized various dimethoxy and methylenedioxy cinnamamide derivatives with tertiary amine groups and evaluated their ability to inhibit cholinesterase and penetrate the blood-brain barrier (BBB).
- Most compounds showed moderate to potent acetylcholinesterase inhibition, with the exception of those containing a morpholine group, and methylenedioxy derivatives displayed better BBB permeability.
- Notably, compound 10c, which has a methylenedioxy and pyrrolidine side chain, demonstrated strong cholinesterase inhibition and reached significant concentrations in brain tissue shortly after administration, indicating its potential for central nervous system drug development.
Article Abstract
In the present investigation, a series of dimethoxy or methylenedioxy substituted-cinnamamide derivatives containing tertiary amine moiety (N. N-Dimethyl, N, N-diethyl, Pyrrolidine, Piperidine, Morpholine) were synthesized and evaluated for cholinesterase inhibition and blood-brain barrier (BBB) permeability. Although their chemical structures are similar, their biological activities exhibit diversity. The results showed that all compounds except for those containing morpholine group exhibited moderate to potent acetylcholinesterase inhibition. Preliminary screening of BBB permeability shows that methylenedioxy substituted compounds have better brain permeability than the others. Compound 10c, containing methylenedioxy and pyrrolidine side chain, showed a better acetylcholinesterase inhibition (IC: 1.52±0.19 μmol/L) and good blood-brain barrier permeability. Further pharmacokinetic investigation of compound 10c using ultra high performance liquid chromatography-mass/mass spectrometry (UPLC-MS/MS) in mice showed that compound 10c in brain tissue reached its peak concentration (857.72±93.56 ng/g) after dosing 30 min. Its half-life in the serum is 331 min (5.52 h), and the C/C at various sampling points is ranged from 1.65 to 4.71(Mean: 2.76) within 24 hours. This investigation provides valuable information on the chemistry and pharmacological diversity of cinnamic acid derivatives and may be beneficial for the discovery of central nervous system drugs.
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| http://dx.doi.org/10.1002/cbdv.202400557 | DOI Listing |
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