Acetylcholinesterase inhibitor and cytotoxic activity of some novel acetazolamide cyclocondensed azetidinones

Abstract

The purpose of the study was to synthesize potent acetylcholinesterase (AChE) inhibitor and cytotoxic compounds by condensing acetazolamide with azetidinones. A new series of novel acetazolamide condensed azetidinones was prepared by Schiff's bases of acetazolamide with chloroacetylchloride in the presence of a catalytic amount of 1,4-dioxane and triethyl amine. Confirmation of the chemical structure of the synthesized compounds (5a–k) was substantiated by melting point, thin layer chromatography, different spectral data infrared, 1 H-nuclear magnetic resonance, and mass spectra. The synthesized compounds were evaluated for AChE inhibitory activity and in vitro cytotoxicity against Vero cells. The titled compounds exhibited weak, moderate, or high AChE inhibitory activity and in vitro cytotoxicity. Compound 5c exhibited potential AChE inhibitory activity, with a concentration of 0.10μM giving 50% inhibition, when compared with the current therapeutic agent donepezil HCl and in vitro cytotoxicity with a lower concentration required to kill 50% of the cells. Acetazolamide-cyclocondensed azetidinones might prove interesting as potential AChE inhibitors and cytotoxic compounds, and should be investigated further.