Synthesis, anticholinesterase activity, molecular docking, and molecular dynamic simulation studies of 1,3,4-oxadiazole derivatives

Abstract

Two new series of 1,3,4-oxadiazoles bearing pyridine and thiazole heterocycles (4a-h and 5a-h) were synthesized (2,5-disubstituted-1,3,4-oxadiazoles). The structures of these newly synthesized compounds were confirmed by ¹ H nuclear magnetic resonance (NMR), ¹³ C NMR, high-resolution mass spectrometric and Fourier transform infrared spectroscopic methods. All these compounds were evaluated for their enzyme inhibitory activities against two cholinesterase enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). From the studies, we identified compounds 4a, 4h, 5a, 5d, and 5e as selective AChE inhibitors, with IC₅₀ values ranging from 0.023 to 0.037 μM. Furthermore, docking studies of these compounds were performed at the active sites of their target enzymes. The molecular docking study showed that 5e possessed an ideal docking pose with interactions inside AChE.

Keywords: anticholinesterase activity; molecular docking; molecular dynamics simulation; oxadiazole; pyridine.