Synthesis and Evaluation of Chroman-4-One Linked to N-Benzyl Pyridinium Derivatives as New Acetylcholinesterase Inhibitors

• Published in: Archiv der Pharmazie (Weinheim) 2015-09, Vol.348 (9), p.643-649
• Main Authors: Arab, Saman, Sadat-Ebrahimi, Seyed-Esmail, Mohammadi-Khanaposhtani, Maryam, Moradi, Alireza, Nadri, Hamid, Mahdavi, Mohammad, Moghimi, Setareh, Asadi, Mehdi, Firoozpour, Loghman, Pirali-Hamedani, Morteza, Shafiee, Abbas, Foroumadi, Alireza
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase; Acetylcholinesterase - chemistry; Acetylcholinesterase - metabolism; Alzheimer's disease; Benzyl Compounds - chemical synthesis; Benzyl Compounds - pharmacology; Cholinesterase Inhibitors - chemical synthesis; Cholinesterase Inhibitors - pharmacology; Chroman-4-one; Docking study; Drug Design; Molecular Docking Simulation; N-Benzyl pyridinium; Protein Conformation; Pyridinium Compounds - chemical synthesis; Pyridinium Compounds - pharmacology; Structure-Activity Relationship
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.201500149

A novel series of chroman‐4‐one derivatives containing the N‐benzyl pyridinium moiety were designed, synthesized, and evaluated for their acetylcholinesterase (AChE) inhibitory activities. Among the various synthesized compounds, (E)‐1‐(2,3‐dibromobenzyl)‐4‐((7‐ethoxy‐4‐oxochroman‐3‐ylidene)methyl)pyridinium bromide (8l) depicted the most potent anti‐AChE activity (IC50 = 0.048 μM). In addition, the molecular modeling study allowed us to detect possible binding modes that are in full compliance with the observed results through in vitro experiments. A novel series of chroman‐4‐one derivatives bearing N‐benzyl pyridinium derivatives (8a–l) were synthesized and evaluated in vitro for their acetylcholinesterase inhibitory activities. The most promising compound, (E)‐1‐(2,3‐dibromobenzyl)‐4‐((7‐ethoxy‐4‐oxochroman‐3‐ylidene)methyl)pyridinium bromide 8l, showed an IC50 value of 0.048 µM.