Benzimidazole-Based Schiff Base Hybrid Scaffolds: A Promising Approach to Develop Multi-Target Drugs for Alzheimer's Disease

A series of benzimidazole-based Schiff base derivatives (1-18) were synthesized and structurally elucidated through 1H NMR, 13C NMR and HREI-MS analysis. Subsequently, these synthetic derivatives were subjected to evaluation for their inhibitory capabilities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). All these derivatives showed significant inhibition against AChE with an IC50 value in the range of 123.9 +/- 10.20 to 342.60 +/- 10.60 mu M and BuChE in the range of 131.30 +/- 9.70 to 375.80 +/- 12.80 mu M in comparison with standard Donepezil, which has IC50 values of 243.76 +/- 5.70 mu M (AChE) and 276.60 +/- 6.50 mu M (BuChE), respectively. Compounds 3, 5 and 9 exhibited potent inhibition against both AChE and BuChE. Molecular docking studies were used to validate and establish the structure-activity relationship of the synthesized derivatives.

Automated summary

A series of benzimidazole-based Schiff base derivatives were synthesized and evaluated for their inhibitory capabilities against acetylcholinesterase and butyrylcholinesterase. Some of the compounds showed potent inhibition and the structure-activity relationship was validated through molecular docking studies.