Synthesis and structure-activity relationship study of benzofuran-based chalconoids bearing benzylpyridinium moiety as potent acetylcholinesterase inhibitors

Manizheh Mostofi; Ghodsi Mohammadi Ziarani; Mohammad Mahdavi; Alireza Moradi; Hamid Nadri; Saeed Emami; Heshmatollah Alinezhad; Alireza Foroumadi; Abbas Shafiee

doi:10.1016/j.ejmech.2015.08.061

Synthesis and structure-activity relationship study of benzofuran-based chalconoids bearing benzylpyridinium moiety as potent acetylcholinesterase inhibitors

Eur J Med Chem. 2015 Oct 20:103:361-9. doi: 10.1016/j.ejmech.2015.08.061. Epub 2015 Sep 3.

Authors

Manizheh Mostofi¹, Ghodsi Mohammadi Ziarani¹, Mohammad Mahdavi², Alireza Moradi³, Hamid Nadri³, Saeed Emami⁴, Heshmatollah Alinezhad⁵, Alireza Foroumadi², Abbas Shafiee⁶

Affiliations

¹ Department of Chemistry, Alzahra University, Vanak Square, P.O. Box 1993891176, Tehran, Iran.
² Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medicinal Sciences, Tehran, Iran.
³ Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
⁴ Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
⁵ Faculty of Chemistry, University of Mazandaran, Babolsar, Iran.
⁶ Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medicinal Sciences, Tehran, Iran. Electronic address: ashafiee@ams.ac.ir.

PMID: 26363872
DOI: 10.1016/j.ejmech.2015.08.061

Abstract

A series of benzofuran-based chalconoids 6a-v were designed and synthesized as new potential AChE inhibitors. The in vitro assay of synthesized compounds 6a-v showed that most compounds had significant anti-AChE activity at micromolar or sub-micromolar levels. Among the tested compounds, 3-pyridinium derivative 6m bearing N-(2-bromobenzyl) moiety and 7-methoxy substituent on the benzofuran ring exhibited superior activity. This compound with IC₅₀ value of 0.027 μM was as potent as standard drug donepezil.

Keywords: Acetylcholinesterase; Alzheimer's disease; Benzofuran; Docking study; Pyridinium.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcholinesterase / metabolism*
Animals
Benzofurans / chemistry*
Chalcones / chemical synthesis
Chalcones / chemistry*
Chalcones / pharmacology*
Cholinesterase Inhibitors / chemical synthesis
Cholinesterase Inhibitors / chemistry*
Cholinesterase Inhibitors / pharmacology*
Dose-Response Relationship, Drug
Electrophorus
Molecular Structure
Pyridinium Compounds / chemical synthesis
Pyridinium Compounds / chemistry*
Pyridinium Compounds / pharmacology
Structure-Activity Relationship

Substances

Benzofurans
Chalcones
Cholinesterase Inhibitors
Pyridinium Compounds
Acetylcholinesterase
benzofuran