Synthesis of ferulic acid derivatives and their inhibition of cholinesterase inhibitory activity

GUAN Li; SONG Xuchao; WANG Xiaoku; ZHAO Ning; LI Weize; WANG Yang

doi:10.11665/j.issn.1000-5048.20220406

Journal of China Pharmaceutical University > 2022 > 53(4): 433-440. > DOI: 10.11665/j.issn.1000-5048.20220406

GUAN Li, SONG Xuchao, WANG Xiaoku, ZHAO Ning, LI Weize, WANG Yang. Synthesis of ferulic acid derivatives and their inhibition of cholinesterase inhibitory activity[J]. Journal of China Pharmaceutical University, 2022, 53(4): 433-440. DOI: 10.11665/j.issn.1000-5048.20220406

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Synthesis of ferulic acid derivatives and their inhibition of cholinesterase inhibitory activity

1.
College of Pharmacy, Xi'an Medical University, Xi'an 710021
2.
Department of Basic Medicine, Xi'an Medical University, Xi'an 710021
3.
Xi'an Municipal Key Laboratory of Pathogenic Microorganisms and Tumor Immunity, Xi'an 710021, China

Funds: This study was supported by the National Natural Science Foundation of China (No.82004075), Shaanxi University Youth Innovation Team Construction Funding Project (Shaanxi Education [2019] No.90), Xi'an Medical University Science and Technology Innovation Team Support (No.2021TDPT04) and the Key Funding for the Provincial Key Discipline Construction Project of Pharmacy (No.2016YXXK01, No.2016YXXK07)

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Received Date: April 13, 2022
Revised Date: May 30, 2022

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Abstract

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..
- ferulic acid,
- derivatives,
- synthesis,
- Alzheimer's disease,
- cholinesterase inhibitor,
- Ellman method

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