Liu_2024_Chem.Biodivers__e202400557

Reference

Title : Discovery of novel cholinesterase inhibitors easily crossing the blood-brain barrier via structure-property relationship investigation: Methylenedioxy-cinnamicamides containing tertiary amine side chain - Liu_2024_Chem.Biodivers__e202400557
Author(s) : Liu HR , Shi Q , Yang ZY , Wang YH , Yi BX , Gao XH , Ding YJ , Peng D , Chen YL
Ref : Chem Biodivers , :e202400557 , 2024
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 (IC50: 1.52+/-0.19 micromol/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 CBrain/CSerum 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.

PubMedSearch : Liu_2024_Chem.Biodivers__e202400557
PubMedID: 38701359

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Citations formats

Liu HR, Shi Q, Yang ZY, Wang YH, Yi BX, Gao XH, Ding YJ, Peng D, Chen YL (2024)
Discovery of novel cholinesterase inhibitors easily crossing the blood-brain barrier via structure-property relationship investigation: Methylenedioxy-cinnamicamides containing tertiary amine side chain
Chem Biodivers :e202400557

Liu HR, Shi Q, Yang ZY, Wang YH, Yi BX, Gao XH, Ding YJ, Peng D, Chen YL (2024)
Chem Biodivers :e202400557