Evaluation of Activity of Some 2,5-Disubstituted Benzoxazole Derivatives against Acetylcholinesterase, Butyrylcholinesterase and Tyrosinase: ADME Prediction, DFT and Comparative Molecular Docking Studies

Abstract

In this study, p-tert-butyl at position 2 and acetamide bridged 4-substituted piperazine/piperidine at position 5 bearing benzoxazole derivatives were evaluated for their in vitro inhibitory activity against AChE, BChE and Tyrosinase, which are important targets in reducing the adverse effects of Alzheimer’s disease. The most active 1 g inhibited the BChE at a concentration of 50 µM by 54 ± 0.75%. Molecular docking studies of the compounds against BChE (PDB: 4BDS) were performed with Schrödinger and AutoDock Vina and the results were compared. Schrödinger docking scores were found to be more consistent. Estimated ADME profiles and bioactivity scores of the compounds were calculated and found to be compatible with Lipinski and other limiting rules. Geometric optimization parameters, MEP analysis and HUMO and LUMO quantum parameters of the most active 1 g were calculated by using DFT/B3LYP theory and 6-311 G (d,p) base set and results was viewed.

Graphical Abstract

Keywords:

• Alzheimer’s disease
• butyrylcholinesterase
• DFT
• MEP
• molecular docking