Biologically Potent Benzimidazole-Based-Substituted Benzaldehyde Derivatives as Potent Inhibitors for Alzheimer's Disease along with Molecular Docking Study.

Twenty-one analogs were synthesized based on benzimidazole, incorporating a substituted benzaldehyde moiety (-). These were then screened for their acetylcholinesterase and butyrylcholinesterase inhibition profiles. All the derivatives except , , and showed various inhibitory potentials, ranging from IC values of 0.050 ± 0.001 µM to 25.30 ± 0.40 µM against acetylcholinesterase, and 0.080 ± 0.001 µM to 25.80 ± 0.40 µM against butyrylcholinesterase, when compared with the standard drug donepezil (0.016 ± 0.12 µM and 0.30 ± 0.010 µM, against acetylcholinesterase and butyrylcholinesterase, respectively). Compound in both cases was found to be the most potent compound due to the presence of chloro groups at the and positions of the phenyl ring. A structure-activity relationship study was performed for all the analogs except , , and , further, molecular dynamics simulations were performed for the top two compounds as well as the reference compound in a complex with acetylcholinesterase and butyrylcholinesterase. The molecular dynamics simulation analysis revealed that compound formed the most stable complex with both acetylcholinesterase and butyrylcholinesterase, followed by compound . As compared to the standard inhibitor donepezil both compounds revealed greater stabilities and higher binding affinities for both acetylcholinesterase and butyrylcholinesterase.