Akincioglu_2015_Bioorg.Med.Chem_23_3592

Reference

Title : Discovery of potent carbonic anhydrase and acetylcholine esterase inhibitors: novel sulfamoylcarbamates and sulfamides derived from acetophenones - Akincioglu_2015_Bioorg.Med.Chem_23_3592
Author(s) : Akincioglu A , Akincioglu H , Gulcin I , Durdagi S , Supuran CT , Goksu S
Ref : Bioorganic & Medicinal Chemistry , 23 :3592 , 2015
Abstract :

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 Ki values in the range of 45.9+/-8.9-687.5+/-84.3 pM for hCA I, and 48.80+/-8.2-672.2+/-71.9pM for hCA II. The inhibitory effects of the synthesized novel compounds on AChE were also investigated. The Ki values of these compounds were in the range of 4.52+/-0.61-38.28+/-6.84pM 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.

PubMedSearch : Akincioglu_2015_Bioorg.Med.Chem_23_3592
PubMedID: 25921269

Related information

Inhibitor CHEMBL3585776

Citations formats

Akincioglu A, Akincioglu H, Gulcin I, Durdagi S, Supuran CT, Goksu S (2015)
Discovery of potent carbonic anhydrase and acetylcholine esterase inhibitors: novel sulfamoylcarbamates and sulfamides derived from acetophenones
Bioorganic & Medicinal Chemistry 23 :3592

Akincioglu A, Akincioglu H, Gulcin I, Durdagi S, Supuran CT, Goksu S (2015)
Bioorganic & Medicinal Chemistry 23 :3592