Design, Synthesis and Biological Evaluation of Novel ۱,۳,۴-Thiadiazol Derivatives as Selective Inhibitors of Butyrylcholinesterase

Butyrylcholinesterase (BChE) is considered a promising drug target which plays an essential part in the progression of the late stage of Alzheimer’s disease (AD). Selective BChE inhibitors could be capable drug candidates for a neurodegenerative disorder. So that, a set of novels ۱,۳,۴-thiadiazole derivatives (۱c-۱۷c) were designed and synthesized in order to selective inhibitory of BChE. Physicochemical and spectroscopic approaches proved the structures of the synthesized compounds, and the purity of the compounds was confirmed by CHN analysis. The compound’s interactions with amino acid residues in the active sites of acetylcholinesterase (AChE) and BChE were examined by in silico molecular docking studies. In vitro cytotoxicity effects measured by MTT method. For evaluating synthetic substances’ inhibitory activity, Ullman's method was used by AChE from electric eel and BuChE from equine serum. Based on the in vitro inhibitory assay results, compounds ۱c (IC۵۰ = ۱۸.۳۴ μM) and ۳c (IC۵۰ = ۱۰.۴۵ μM) exhibited inhibitory potency on BChE. Results indicate that these compounds (۱c and ۳c) possibly will be subjected to further investigations. The present study may be hoped to stimulate efforts to develop of novel BChE inhibitor agents.

Keywords:

Heterocyclic compounds , Thiadoazole , Bioorganic chemistry , Computational chemistry , Drug research