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Synthesis and Biological Activity of Some Benzochromenoquinolinones: Tacrine Analogs as Potent Anti‐Alzheimer's Agents
Author(s) -
Mahdavi Mohammad,
Hariri Roshanak,
Mirfazli Seyedeh Sara,
Lotfian Hania,
Rastergari Arezoo,
Firuzi Omidreza,
Edraki Najmeh,
Larijani Bagher,
Akbarzadeh Tahmineh,
Saeedi Mina
Publication year - 2019
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201800488
Subject(s) - tacrine , butyrylcholinesterase , acetylcholinesterase , chemistry , cholinesterase , pharmacology , aché , neuroprotection , ic50 , docking (animal) , inhibitory postsynaptic potential , alzheimer's disease , lead compound , drug , biochemistry , stereochemistry , enzyme , disease , in vitro , medicine , nursing
Alzheimer's disease (AD) is a well‐known neurodegenerative disorder affecting millions of old people worldwide and the corresponding epidemiological data emphasize the importance of the disease. As AD is a multifactorial illness, various single target directed drugs that have reached clinical trials have failed. Therefore, various factors associated with outset of AD have been considered in targeted drug discovery. In this work, various benzochromenoquinolinones were synthesized and evaluated for their cholinesterase and BACE1 inhibitory activities as well as neuroprotective and metal‐chelating properties. Among the synthesized compounds, 14‐amino‐13‐(3‐nitrophenyl)‐2,3,4,13‐tetrahydro‐1 H ‐benzo[6,7]chromeno[2,3‐ b ]quinoline‐7,12‐dione ( 6m ) depicted the best inhibitory activity toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC 50 s of 0.86 and 6.03 μ m , respectively. Also, the compound could inhibit β ‐secretase 1 (BACE1) with IC 50 =19.60 μ m and showed metal chelating ability toward Cu 2+ , Fe 2+ , and Zn 2+ . In addition, docking study demonstrated desirable interactions of compound 6m with amino acid residues characterizing AChE, BChE, and BACE1.