Abstract
To discover multifunctional agents for the treatment of Alzheimer's disease, a series of hydrazide based Schiff bases were designed and synthesized based on multitarget-directed strategy. We have synthesized twenty-eight analogs of hydrazide based Schiff bases, characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase and butyrylcholinesterase inhibition. All compounds showed varied degree of acetylcholinesterase and butyrylcholinesterase inhibition when compared with standard Eserine. Among the series, compounds 10, 3 and 24 having IC50 values 4.12 +/- 0.01, 8.12 +/- 0.01 and 8.41 +/- 0.06 mu M respectively showed potent acetylcholinesterase inhibition when compared with Eserine (IC50 = 0.85 +/- 0.0001 mu M). Three compounds 13, 24 and 3 having IC50 values 6.51 +/- 0.01, 9.22 +/- 0.07 and 37.82 +/- 0.14 mu M respectively showed potent butyrylcholinesterase inhibition by comparing with eserine (IC50 = 0.04 +/- 0.0001 mu M). The remaining compounds also exhibited moderate to weak inhibitory potential. Structure activity relationship has been established. Through molecular docking studies the binding interaction was confirmed. (C) 2016 Elsevier Inc. All rights reserved.