Synthesis and In vitro Evaluation of Thiadiazole Derivatives as AChE, BuChE and LOX Inhibitors

Abstract

N'-Benzylidene-2-[[5-(phenylamino)-1,3,4-thiadiazol-2-yl]thio]acetohydrazide derivatives (5a-p) were synthesized to screen for their AChE, BuChE and LOX inhibitory activity. The CCK-8 assay was also carried out to determine their cytotoxicity against NIH/3T3 cells. The most potent AChE inhibitors were found as compounds 5m (49.79% +/- 3.08) and 5p (42.39% +/- 3.19), whereas the most potent BuChE inhibitor was found as compound 5d (35.15% +/- 2.21). Among these derivatives, N'-(3-methoxybenzylidene)-2-[[5-(phenylamino)-1,3,4-thiadiazol-2-yl]thio]acetohydrazide (5p) can be considered as the most promising AChE inhibitor due to its low cytotoxicity to NIH/3T3 cells (IC50 > 500 mu g/mL). N'-(4-Methoxybenzylidene)- 2-[[5-(phenylamino)-1,3,4-thiadiazol-2-yl]thio]a-cetohydrazide (5n) exhibited weak inhibition on LOX (% 20.65 +/- 0.08), whilst the other compounds were not active.