Novel tetrazole derivatives: synthesis, anticholinesterase activity and cytotoxicity evaluation

Abstract

Objective(s): The synthesis of new N'-arylidene-4-[(1phenyl- 1H-tetrazole-5-yl) thio] butanoylhydrazide derivatives (1-26) and investigation of their potential anticholinesterase (AChE), butyrylcholinesterase (BuChE) enzyme inhibition activities and also cytotoxic properties on mouse embryonic fibroblast cells (NIH/3T3) were aimed in this work. Materials and methods: The target compounds were prepared by a three step synthetic procedure using 1-phenyl1H- tetrazole-5-thiol and ethyl 4-chlorobutanoate as starting materials. The structures of the obtained compounds were elucidated by IR, H-1-NMR, C-13-NMR spectra and elemental analysis data. The enzyme inhibition and cytotoxic activities were determined according to Ellman and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] methods, respectively. Results: Compounds 14, 15 and compound 18 exhibited the highest inhibitory activity on AChE and BuChE enzymes. Additionally, compounds 4, 5, 8 and 16 exhibited the lowest cytotoxicity against NIH/3T3 cells. Conclusion: Compounds 14, 15 and 18 bearing 2-nitro, 3-nitro and 3-hydroxy substituents have showed selective enzyme inhibitory activities.