Hetero-annulated coumarins as new AChE/BuChE inhibitors

synthesis and biological evaluation

Seyed Esmaeil Sadat Ebrahimi, Pegah Ghadirian, Hamideh Emtiazi, Azadeh Yahya-Meymandi, Mina Saeedi, Mohammad Mahdavi, Hamid Nadri, Alireza Moradi, Bilqees Sameem, Mohsen Vosooghi, Saeed Emami, Alireza Foroumadi, Abbas Shafiee*

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

A series of chromene-fused coumarins known as 10,11-dihydrochromeno[4,3-b]chromene-6,8(7H,9H)-diones 4a–o were synthesized through one-pot reaction of appropriate benzaldehydes, dimedone, and 4-hydroxycoumarin in the presence of nano-silica sulfuric acid under solvent-free condition in good yields. The in vitro anticholinesterase assay revealed that the 3-hydroxyphenyl analog 4e showed the highest inhibitory activity against both acetylcholinesterase and butyrylcholinesterase, possessing IC 50 values of 3.28 and 2.19 µM, respectively. The structure-activity relationships study demonstrated that the selectivity for acetylcholinesterase over butyrylcholinesterase could be modulated by introducing second hydroxyl or methoxy substituent on the para-position of the 3-hydroxyphenyl pendent group. The docking study of compound 4e with acetylcholinesterase confirmed π–π stacking interaction between the coumarin moiety and Trp279 as well as the formation of hydrogen bonding between hydroxyl group and Asn85.

Original languageEnglish
Pages (from-to)1831-1841
Number of pages11
JournalMedicinal Chemistry Research
Volume25
Issue number9
DOIs
Publication statusPublished - 1 Sep 2016
Externally publishedYes

Keywords

  • acetylcholinesterase
  • Alzheimer’s disease
  • coumarin-fused derivatives
  • multicomponent reactions
  • one-pot synthesis

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