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Synthesis and Biological Activity of Some Benzochromenoquinolinones: Tacrine Analogs As Potent Anti-Alzheimer's Agents Publisher Pubmed



Mahdavi M1 ; Hariri R2 ; Mirfazli SS3 ; Lotfian H2 ; Rastergari A2 ; Firuzi O4 ; Edraki N4 ; Larijani B1 ; Akbarzadeh T2, 5 ; Saeedi M5, 6
Authors

Source: Chemistry and Biodiversity Published:2019


Abstract

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-1H-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 μm, respectively. Also, the compound could inhibit β-secretase 1 (BACE1) with IC 50 =19.60 μm 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. © 2019 Wiley-VHCA AG, Zurich, Switzerland
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