Title : Synthesis, evaluation and computational simulation of novel coumarin derivatives as potential acetylcholinesterase inhibitors
Alzheimer’s disease (AD) is characterized by a slow but progressive deterioration in cognitive performance. The decrease of acetylcholine (ACh) due to cholinergic neuronal dysfunction in the hippocampus and cortex could result in AD. Current clinical therapy for AD patients is mainly palliative treatment targeting acetylcholinesterase (AChE). Novel coumarin derivatives were designed using the fragment-based drug design. Hybridization of the acetylcholine backbone with the coumarin scaffold provides coumarin-3-carboxylates and 3-carboxamides with rigid aza(mono,bi)cyclic structures. Several coumarin derivatives exhibited much stronger AChE inhibitory activities compared to those of donepezil both in vitro and in vivo. Computational simulation studies were performed in order to gain insights into the possible binding modes of the derivatives.
Audience take away:
• Alzheimer’s disease (AD) : etiology, pathophysiology, misc
• Fragment-based drug design
• Drug discovery trends in AD
• Problems of drug development in this area (AD)
• Computational Simulation to get possible mode of bindings