Discovery of potent carbonic anhydrase and acetylcholine esterase inhibitors: Novel sulfamoylcarbamates and sulfamides derived from acetophenones

In this study, several novel sulfamides were synthesized and evaluated for their acetylcholine esterase (AChE) and human carbonic anhydrase I, and II isoenzymes (hCA I and II) inhibition profiles. Reductive amination of methoxyacetophenones was used for the synthesis of amines. Amines were converted to sulfamoylcarbamates with chlorosulfonyl isocyanate (CSI) in the presence of BnOH. Pd-C catalyzed hydrogenolysis of sulfamoylcarbamates afforded sulfamides. These novel compounds were good inhibitors of the cytosolic hCA I, and hCA II with K-i values in the range of 45.9 +/- 8.9-687.5 +/- 84.3 pM for hCA I, and 48.80 +/- 8.2-672.2 +/- 71.9 pM for hCA II. The inhibitory effects of the synthesized novel compounds on AChE were also investigated. The K-i values of these compounds were in the range of 4.52 +/- 0.61-38.28 +/- 6.84 pM for AChE. These results show that hCA I, II, and AChE were effectively inhibited by the novel sulfamoylcarbamates 17-21 and sulfamide derivatives 22-26. All investigated compounds were docked within the active sites of the corresponding enzymes revealing the reasons of the effective inhibitory activity. (C) 2015 Elsevier Ltd. All rights reserved.