New Imidazo[1,2-a]pyridin-2-yl Derivatives as AChE, BChE, and LOX Inhibitors; Design, Synthesis, and Biological Evaluation

Background: Inhibition of cholinesterase enzyme has been recognized as an important target in the symptomatic treatment of Alzheimer’s disease. Objective: In the current work, a series of new N-(4-(imidazo[1,2-a]pyridin-2-yl)phenyl)cinnamamide derivatives were synthesized and their inhibitory activities against acetyl cholinesterase, butrylcholinesterase, and Lipoxygenase were evaluated. Methods: The target compounds were synthesized as the literature reported with some modifications. The AChE, BChE, and LOX inhibitory activities of the synthesized compounds were evaluated using in vitro methods. The docking and kinetic studies were performed for the most potent compounds to evaluate the inhibition mechanism. Results: The structural elucidation of the synthesized imidazo-pyridine derivatives was performed by different spectroscopic techniques including IR, NMR, and Mass. Most of the synthesized compounds demonstrated good AChE, BChE, and LOX inhibitory activities. The most active AChE, BChE, and sLOX-1 inhibitors were found for compounds 4a, 4g, and 4l, respectively. The docking study also revealed that the three compounds, 4a, 4g, and 4l, have important binding interactions with the AChE, BChE, and sLOX-1 enzyme active sites, respectively. Conclusion: The results of current study shows imidazo[1,2-a]pyridine derivatives have potential for development of novel drug candidate for AD as AChE, BChE and sLOX-1 inhibitors.