Akincioglu_2017_Bioorg.Chem_74_238

Reference

Title : The synthesis of novel sulfamides derived from beta-benzylphenethylamines as acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase enzymes inhibitors - Akincioglu_2017_Bioorg.Chem_74_238
Author(s) : Akincioglu A , Kocaman E , Akincioglu H , Salmas RE , Durdagi S , Gulcin I , Supuran CT , Goksu S
Ref : Bioorg Chem , 74 :238 , 2017
Abstract :

In this study, a series of novel beta-benzylphenethylamines and their sulfamide derivatives were synthesized starting from (Z)-2,3-diphenylacrylonitriles. Pd-C catalysed hydrogenation of diphenylacrylonitriles, reduction of propanenitriles with LiAlH4 in the presence of AlCl3 followed by addition of conc. HCl afforded beta-benzylphenethylamine hydrochloride salts. The reactions of these amine hydrochloride salts with chlorosulfonyl isocyanate (CSI) in the presence of tert-BuOH and excess Et3N gave sulfamoylcarbamates. Removing of Boc group from the synthesized sulfamoylcarbamates with trifluoroacetic acid (TFA) yielded novel sulfamides in good yields. These novel sulfamides derived from beta-benzylphenethylamines were effective inhibitors of the cytosolic carbonic anhydrase I and II isoenzymes (hCA I and II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with Ki values in the range of 0.278-2.260nM for hCA I, 0.187-1.478nM for hCA II, 0.127-2.452nM for AChE and 0.494-1.790nM for BChE. The inhibitory effects of the synthesized novel sulfamides derived from beta-benzylphenethylamines were compared to those of acetazolamide and dorzolamide as clinical hCA I and II isoenzymes inhibitors and tacrine as a clinical AChE and BChE enzymes inhibitors. In addition to in vitro tests, molecular modeling approaches are implemented not only for prediction of the binding affinities of the compounds but also to study their inhibition mechanisms in atomic level at the catalytic domains.

PubMedSearch : Akincioglu_2017_Bioorg.Chem_74_238
PubMedID: 28866249

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Citations formats

Akincioglu A, Kocaman E, Akincioglu H, Salmas RE, Durdagi S, Gulcin I, Supuran CT, Goksu S (2017)
The synthesis of novel sulfamides derived from beta-benzylphenethylamines as acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase enzymes inhibitors
Bioorg Chem 74 :238

Akincioglu A, Kocaman E, Akincioglu H, Salmas RE, Durdagi S, Gulcin I, Supuran CT, Goksu S (2017)
Bioorg Chem 74 :238