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

Abstract

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 µM) 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 µM) 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 µM) 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 ¹H-NMR, ¹³C-NMR and HREI-MS, respectively.

Communicated by Ramaswamy H. Sarma

Keywords:

• Acetylcholinesterase
• benzo[d]oxazole
• synthesis
• bis Schiff base
• butyrylcholinesterase
• molecular docking
• SAR

Acknowledgements

We thank the Higher education commission (HEC) of Pakistan for funding a research grant and basic facilities to synthesize heterocyclic moieties in search of lead molecules under the National Research Program for University under Project No. 5721 and 5092.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

We thank the Higher education commission (HEC) of Pakistan for funding a research grant and basic facilities to synthesize heterocyclic moieties in search of lead molecules under the National Research Program for University under Project No. 5721 and 5092.