Design, Synthesis And Biological Evaluation Of Substituted Oxadiazole Derivatives As New Scaffolds Against Butyrylcholinesterase

Abstract

Novel anti-butyrylcholinesterase inhibitors containing, oxadiazole derivatives, were designed and these molecules were subjected to molecular docking study. The docking study revealed that the designed compounds possess significant to moderate interaction with the targeted enzyme butyrylcholinesterase. Among them compound 3 (10.5 K/cal) and 6 (10.2K/cal) showed similar docking compared to donepezil (12.76 K/cal). Remaining compounds show good to moderate activity compared to standard drug. The target compounds were evaluated for their inhibitory activity against the BuChE. Among these new derivatives, 3 (53.85±4.2 nM) was found to inhibit cholinesterase catalyticdomain most significantly, and then compound 51 (39.39±5.4nM) possessed significant cholinesterase inhibitory activity. Compound 3 and 51 have more inhibitory activity than the remaining tested compounds.This may be due to the presence of more electronegative atoms (Cl) in the substitution. Of these compounds, compound 2 (53.85±4.2 nM) have moderate inhibitory activity against cholinesterase. The remaining tested compoundshave moderate to good inhibitory activity against the cholinesterase enzyme. In addition, ADMET prediction results indicated that these compounds might be less toxic and display more interesting pharmacokinetic properties.