Design, Synthesis and Cholinesterase Inhibitory Activity of Novel 1,3,4-Thiadiazole Derivatives

Abstract

Inhibition of the cholinesterases (AChE and BChE) plays a pivotal role in the symptomatic treatment of Alzheimer’s disease. The present study reports the synthesis and anticholinesterase activity of five novel thiadiazole analogs in search of anti-Alzheimer agents. The structures of the newly synthesized compounds were characterized using 1H NMR, 13C NMR and HRMS. Tested compounds inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes with IC50 values in the range of 8.250-20.382 μM and 14.143-0.986 μM, respectively. N-(4-Chlorophenyl)-2-[(5-(allylamino)-1,3,4-thiadiazol-2-yl)thio]-N-(3-nitrobenzyl)acetamide (6e) was determined as the most potent inhibitor against both tested enzymes when compared with standard drug tacrine. Molecular docking study was carried out to reveal the binding interactions between compound 6e and the active site of AChE