[3 + 2] Cycloaddition Synthesis of New (Chromene-1,3,4-Oxadiazole) Hybrids Linked to Pyrazole Units as Potential Acetylcholinesterase Inhibitors

A lot of interest has been gained recently in developing novel acetylcholinesterase (AChE) inhibitors that can alleviate Alzheimer's symptoms. In the current study, we aimed to explore AChE inhibitory activity of new chromenes attached to 1,3,4-oxadiazole and/or pyrazole units. The new hybrids were obtained via [3 + 2] cycloaddition reaction between the appropriate chromene-based enaminones and hydrazonyl chlorides. The inhibition percentages of the new products against AChE were recorded at tested concentrations of 15 and 25 µM compared to donepezil. 3-(3-Acetyl-1-(4-methoxyphenyl)-1H-pyrazole-4-carbonyl)-6-(((5-phenyl-1,3,4-oxadiazol-2-yl)thio)methyl)-2H-chromen-2-one displayed promising activity with inhibition percentages of 73.2 and 87.3, respectively, at the aforementioned concentrations. Moreover, the previous hybrid gave promising 2,2-diphenylpicrylhydrazyl (DPPH) inhibitory activity using the reference ascorbic acid. It had an inhibition percentage of 86.6 at a tested concentration of 25 µM.