Synthesis, in vitro biological screening and docking study of benzo[d]oxazole bis Schiff base derivatives as a potent anti-Alzheimer agent

We have synthesized benzo[d]oxazole derivatives (1-21) through a multistep reaction. Alteration in the structure of derivatives was brought in the last step via using various substituted aromatic aldehydes. In search of an anti-Alzheimer agent, all derivatives were evaluated against acetylcholinesterase and butyrylcholinesterase enzyme under positive control of standard drug donepezil (IC50 = 0.016 +/- 0.12 and 4.5 +/- 0.11 mu M) respectively. In case of acetylcholinesterase enzyme inhibition, derivatives 8, 9 and 18 (IC50 = 0.50 +/- 0.01, 0.90 +/- 0.05 and 0.3 +/- 0.05 mu M) showed very promising inhibitory potentials. While in case of butyrylcholinesterase enzyme inhibition, most of the derivatives like 6, 8, 9, 13, 15, 18 and 19 (IC50 = 2.70 +/- 0.10, 2.60 +/- 0.10, 2.20 +/- 0.10, 4.25 +/- 0.10, 3.30 +/- 0.10, 0.96 +/- 0.05 and 3.20 +/- 0.10 mu M) displayed better inhibitory potential than donepezil. Moreover, derivative 18 is the most potent one among the series in both inhibitions. The binding interaction of derivatives with the active gorge of the enzyme was confirmed via a docking study. Furthermore, the binding interaction between derivatives and the active site of enzymes was correlated through the SAR study. Structures of all derivatives were confirmed through spectroscopic techniques such as H-1-NMR, C-13-NMR and HREI-MS, respectively. Communicated by Ramaswamy H. Sarma

Automated summary

A series of benzo[d]oxazole derivatives were synthesized through a multistep reaction, with the alteration in structure being made via the use of various substituted aromatic aldehydes. These derivatives were evaluated for their inhibitory potential against acetylcholinesterase and butyrylcholinesterase enzymes. Derivative 18 showed the most promising inhibitory potential and its binding interaction with the enzyme's active gorge was confirmed through a docking study. The structural confirmation of all derivatives was done using spectroscopic techniques such as H-1-NMR, C-13-NMR, and HREI-MS.