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Design and synthesis of 2,4‐dioxochroman‐pyridinium‐phenylacetamide derivatives as new anti‐Alzheimer agents: in vitro and in silico studies
Author(s) -
Mollazadeh Marjan,
MohammadiKhanaposhtani Maryam,
Azizian Homa,
Zonouzi Afsaneh,
Abdolahi Zahra,
Nadri Hamid,
Larijani Bagher,
Biglar Mahmood,
Mahdavi Mohammad
Publication year - 2020
Publication title -
journal of the chinese chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.329
H-Index - 45
eISSN - 2192-6549
pISSN - 0009-4536
DOI - 10.1002/jccs.202000013
Subject(s) - chemistry , butyrylcholinesterase , pyridinium , acetylcholinesterase , cholinesterase , in silico , in vitro , aché , cytotoxicity , enzyme , donepezil , molecular model , stereochemistry , combinatorial chemistry , biochemistry , organic chemistry , pharmacology , medicine , gene , dementia , disease , pathology
2,4‐Dioxochroman‐pyridinium‐phenylacetamide derivatives 7a–n were synthesized and evaluated for their in vitro cholinesterase (ChE) inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Obtained results demonstrated that, among the synthesized compounds, two compounds, 7j and 7k , were more potent than the standard drug donepezil against BuChE and did not show cytotoxicity and carcinogenicity. Furthermore, through molecular modeling and molecular dynamic studies. we showed that these compounds can be located deep in the gorge cavity of BuChE and that they interacted with catalytic residues, acyl, and cholin‐binding pockets of this enzyme. Support information