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

doi:10.1007/s00044-016-1626-7

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 journal › Article

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 language	English
Pages (from-to)	1831-1841
Number of pages	11
Journal	Medicinal Chemistry Research
Volume	25
Issue number	9
DOIs	https://doi.org/10.1007/s00044-016-1626-7
Publication status	Published - 1 Sep 2016
Externally published	Yes

Keywords

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

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10.1007/s00044-016-1626-7

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Ebrahimi, Seyed Esmaeil Sadat ; Ghadirian, Pegah ; Emtiazi, Hamideh ; Yahya-Meymandi, Azadeh ; Saeedi, Mina ; Mahdavi, Mohammad ; Nadri, Hamid ; Moradi, Alireza ; Sameem, Bilqees ; Vosooghi, Mohsen ; Emami, Saeed ; Foroumadi, Alireza ; Shafiee, Abbas. / Hetero-annulated coumarins as new AChE/BuChE inhibitors : synthesis and biological evaluation. In: Medicinal Chemistry Research. 2016 ; Vol. 25, No. 9. pp. 1831-1841.

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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.",

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Hetero-annulated coumarins as new AChE/BuChE inhibitors : synthesis and biological evaluation. / Ebrahimi, Seyed Esmaeil Sadat; Ghadirian, Pegah; Emtiazi, Hamideh; Yahya-Meymandi, Azadeh; Saeedi, Mina; Mahdavi, Mohammad; Nadri, Hamid; Moradi, Alireza; Sameem, Bilqees; Vosooghi, Mohsen; Emami, Saeed; Foroumadi, Alireza; Shafiee, Abbas.

In: Medicinal Chemistry Research, Vol. 25, No. 9, 01.09.2016, p. 1831-1841.

Research output: Contribution to journal › Article

TY - JOUR

T1 - Hetero-annulated coumarins as new AChE/BuChE inhibitors

T2 - synthesis and biological evaluation

AU - Ebrahimi, Seyed Esmaeil Sadat

AU - Ghadirian, Pegah

AU - Emtiazi, Hamideh

AU - Yahya-Meymandi, Azadeh

AU - Saeedi, Mina

AU - Mahdavi, Mohammad

AU - Nadri, Hamid

AU - Moradi, Alireza

AU - Sameem, Bilqees

AU - Vosooghi, Mohsen

AU - Emami, Saeed

AU - Foroumadi, Alireza

AU - Shafiee, Abbas

PY - 2016/9/1

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N2 - 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.

AB - 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.

KW - acetylcholinesterase

KW - Alzheimer’s disease

KW - coumarin-fused derivatives

KW - multicomponent reactions

KW - one-pot synthesis

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DO - 10.1007/s00044-016-1626-7

M3 - Article

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JO - Medicinal Chemistry Research

JF - Medicinal Chemistry Research

SN - 1054-2523

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