Carbonic anhydrase inhibitory properties of novel benzylsulfamides using molecular modeling and experimental studies

GÖKSU S., NADERI A., Akbaba Y., KALIN P., Akincioglu A., GÜLÇİN İ., ...Daha Fazla

BIOORGANIC CHEMISTRY, cilt.56, ss.75-82, 2014 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 56
  • Basım Tarihi: 2014
  • Doi Numarası: 10.1016/j.bioorg.2014.07.009
  • Dergi Adı: BIOORGANIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.75-82
  • Anahtar Kelimeler: Benzyl amine, Carbonic anhydrase, Enzyme inhibition, Sulfamide, Sulfamoyl carbamate, Molecular modeling, INCLUDING NATURAL-PRODUCTS, ERYTHROCYTE ISOZYMES I, ZINC COORDINATION, ISOFORMS I, DERIVATIVES, VITRO, ISOENZYMES, PROTEIN, ENZYME, SULFAMIDES
  • Atatürk Üniversitesi Adresli: Evet

Özet

In this study, a series of sulfamoyl carbamates and sulfamide derivatives were synthesized. Six commercially available benzyl amines and BnOH were reacted with chlorosulfonyl isocyanate (CSI) to give sulfamoyl carbamates. Pd-C catalyzed hydrogenolysis reactions of carbamates afforded sulfamides. The inhibition effects of novel benzylsulfamides on the carbonic anhydrase I, and II isoenzymes (CA I, and CA II) purified from fresh human blood red cells were determined by Sepharose-4B-L-Tyrosine-sulfanilamide affinity chromatography. In vitro studies were shown that all of novel synthesized benzylsulfamide analogs inhibited, concentration dependently, both hCA isoenzyme activities. The novel benzylsulfamide compounds investigated here exhibited nanomolar inhibition constants against the two isoenzymes. K-i values were in the range of 28.48 +/- 0.01-837.09 +/- 0.19 nM and 112.01 +/- 0.01-268.01 +/- 0.22 nM for hCAI and hCA II isoenzymes, respectively. Molecular modeling approaches were also applied for studied compounds. (C) 2014 Elsevier Inc. All rights reserved.