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

Akincioglu A., Akincioglu H., GÜLÇİN İ., Durdagi S., SUPURAN C. T., GÖKSU S.

BIOORGANIC & MEDICINAL CHEMISTRY, cilt.23, sa.13, ss.3592-3602, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 23 Sayı: 13
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1016/j.bmc.2015.04.019
  • Dergi Adı: BIOORGANIC & MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.3592-3602
  • Anahtar Kelimeler: Acetylcholine esterase, Carbonic anhydrase, Enzyme inhibition, Hybrid molecules, Sulfamide, Sulfamoylcarbamate, Molecular docking, ERYTHROCYTE ISOZYMES I, REDUCTIVE AMINATION, ALZHEIMERS-DISEASE, CHOLINESTERASE INHIBITOR, SULFONAMIDE DERIVATIVES, BIOLOGICAL EVALUATION, NATURAL-PRODUCTS, VITRO, ANTIOXIDANT, RIVASTIGMINE
  • Atatürk Üniversitesi Adresli: Evet

Özet

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.