The synthesis of novel sulfamides derived from beta-benzylphenethylamines as acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase enzymes inhibitors

AKıNCıOĞLU A., KOCAMAN E., Akincioglu H., Salmas R. E., Durdagi S., GÜLÇİN İ., ...Daha Fazla

BIOORGANIC CHEMISTRY, cilt.74, ss.238-250, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 74
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1016/j.bioorg.2017.08.012
  • Dergi Adı: BIOORGANIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.238-250
  • Anahtar Kelimeler: Acetylcholinesterase, Butyrylcholinesterase, Carbonic anhydrase, Phenethylamines, Sulfamide, Sulfamoylcarbamate, Molecular modeling, Molecular docking simulations, ISOENZYMES HCA I, X-RAY STRUCTURES, BIOLOGICAL EVALUATION, ESTERASE INHIBITORS, ANTICHOLINERGIC PROPERTIES, BENZYLAMINE DERIVATIVES, BROMOPHENOL DERIVATIVES, SULFONAMIDE DERIVATIVES, ALZHEIMERS-DISEASE, ANTIOXIDANT
  • Atatürk Üniversitesi Adresli: Evet

Özet

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 K-i values in the range of 0.278-2.260 nM for hCA I, 0.187-1.478 nM for hCA II, 0.127-2.452 nM for AChE and 0.494-1.790 nM 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. (C) 2017 Elsevier Inc. All rights reserved.