1. Hetero-annulated coumarins as new AChE/BuChE inhibitors: synthesis and biological evaluation
- Author
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Mohsen Vosooghi, Azadeh Yahya-Meymandi, Mohammad Mahdavi, Bilqees Sameem, Saeed Emami, Pegah Ghadirian, Abbas Shafiee, Hamid Nadri, Seyed Esmaeil Sadat Ebrahimi, Alireza Foroumadi, Hamideh Emtiazi, Mina Saeedi, and Alireza Moradi
- Subjects
010405 organic chemistry ,Stereochemistry ,Organic Chemistry ,Substituent ,010402 general chemistry ,Coumarin ,01 natural sciences ,Acetylcholinesterase ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Docking (molecular) ,Dimedone ,Moiety ,General Pharmacology, Toxicology and Pharmaceutics ,Selectivity ,Butyrylcholinesterase - 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 IC50 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.
- Published
- 2016
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