New multifunctional agents and their inhibitory effects on the acetyl cholinesterase enzyme

Abstract

A novel series of 2-((-1-substituted phenyl-1H-tetrazol-5-yl)thio)-2,3-dihydro-1H-inden-1-one compounds were designed, synthesized, and evaluated as multi-potent anti-Alzheimer drug candidates. First, treatment of various organic isothiocyanates with sodium azide in the presence of pyridine gave corresponding 1-substituted phenyl-1H-tetrazol-5-thiol compounds. Then, novel 2-((-1-substituted phenyl-1H-tetrazol-5-yl)thio)-2,3-dihydro-1H-inden-1-one compounds were synthesized by treatment of 2,3-dihydro-1H-inden-1-one with the 1-substituted phenyl-1H-tetrazol-5-thiol in the presence of I2. The synthesized compounds were characterized by spectroscopic methods. The inhibitory effects of the synthesized compounds on the acetyl cholinesterase enzyme (AChE) were then tested. An o-iodo substituent displayed higher activity compared to the other analogs. The o-iodo substituent showed a mixed-type of the AChE with an IC50 value of 1.75 μM. For the studied compunds all IC50 values for AChE were in the micromolar range.

Keywords

• alzheimer's disease, tetrazole, inhibition