Microwave-based synthesis of novel generation tacrine-solfonami̇de compounds that could be drug for treating alzheimer's disease and assesment of inhibition applications on cholinesterase isoenzymes

In This study, novel aldehyde, chromene and tacrine compounds containing sulfonamide groups were synthesized. The cholinesterase inhibitors, which are more probable to be effective for Alzheimer's treatment, were obtained with the synthesis of these compounds. At the first stage, 4-sulfamoylbenzoic acid was converted to 4-sulfamoylbenzoyl chloride in SOCl2 with assisted microwave irritation. At the second stage, novel aldehyde-sulfonamide compounds were obtained with interactions of hydroxybenzaldehydes and 4-sulfamoylbenzoyl chloride. In the third step, the novel cromene-sulfonamide compounds were synthesized by enabling the aldehyde-sulfonamides, malononitrile, and dimedone compounds interact to each other with assisted microwave irritation. Then, the tacrine-sulfonamides were obtained between the new cromene-sulfonamide compounds and the cyclic ketone compounds (cyclopentanone, cyclohexanone, cycloheptanone) with the help of microwave irritation. The obtained new products were purified using column chromatography. The structures of the synthesized compounds were characterized by using spectroscopic methods (IR, 1H-NMR, 13C-NMR (APT) and HRMS). The inhibition effect of these compounds on cholinesterase enzymes were investigated according to Ellman's method. Among the synthesized compounds, 4-(11-amino-3,3-dimethyl-1-oxo-2,3,4,7,8,9,10,12-octahydro-1H-chromeno[2,3-b]quinolin-12-yl)phenyl 4-sulfamoylbenzoate (VIIIf, IC50=0.009 μM) for AChE, 4-(2-amino-3-cyano-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromen-4-yl)phenyl 4-sulfamoylbenzoate (VIIb, IC50= 0,243 μM) for BuChE were found to be the most active ones. Also, structure–activity relationships were investigated and the effects of different substituents and their binding positions on the enzyme inhibition were discussed.