molecular docking, synthesis and biological screening of some novel benzothiazoles as acetylcholinesterase inhibitors

Alzheimer’s disease (ad) is a progressive neurodegenerative disorder that is characterized by memory loss and cognitive decline. current therapies for ad primarily address symptoms rather than modify disease progression. in this study, novel benzothiazole derivatives bearing an azetidinone ring were designed, synthesized, and evaluated as potential ache inhibitors through molecular docking studies followed by wet lab synthesis and evaluation of their anti-alzheimer in vitro screening. computational studies, such as molecular docking of benzothiazole derivatives with their protein targets, were performed to design compounds with potential anti-ad activity. subsequently, wet lab synthesis of azetidinone derivatives was conducted. derivatization of the amino group was achieved by treating the parent compound riluzole with various aldehydes to afford 3-chloro-4-aryl-1-[6-(trifluoromethoxy)-benzothiazol-2-yl]-azetidin-2-ones. all the synthesized derivatives were characterized and tested for their in vitro ache inhibitory activity using elman’s assay method. docking studies revealed that some of the derivatives demonstrated significantly stronger binding affinities than the known reference anti-ad drug riluzole. while riluzole exhibited a binding energy of -6.6 kcal/mol, compounds 4b and 4i showed significantly lower binding energies of -11.27 kcal/mol and -11.21 kcal/mol, respectively. in vitro ache inhibition by compound 4b exhibited an ic50 value of 679.896 μg/ml, and derivative 4i was found to be the second most potent with an ic50 value of 685.236 μg/ml compared to the known reference riluzole, which had an ic50 value of 801.157 μg/ml. thus, the docking and bioassay results suggest that compounds 4b and 4i could serve as promising leads with therapeutic potential for the management of ad.