Synthesis and carbonic anhydrase inhibitory properties of novel 4-(2-aminoethyl)benzenesulfonamide-dipeptide conjugates

KÜÇÜKBAY H., Bugday N., Kucukbay F. Z., Berrino E., Bartolucci G., Del Prete S., ...Daha Fazla

BIOORGANIC CHEMISTRY, cilt.83, ss.414-423, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 83
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1016/j.bioorg.2018.11.003
  • Dergi Adı: BIOORGANIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.414-423
  • Anahtar Kelimeler: Carbonic anhydrase, Inhibitor, Sulfonamide, Dipeptide, Conjugate, BINDING-SITE, AMINO-ACID, SULFONAMIDES, XII, IX, ANTIBACTERIAL, BIOASSAY, DESIGN
  • İnönü Üniversitesi Adresli: Evet

Özet

Thirty novel sulfonamide derivatives incorporating dipeptide were synthesized by facile acylation through benzotriazole mediated reactions and their structures were identified by H-1 NMR, C-13 NMR, MS and FT-IR spectroscopic techniques and elemental analysis. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against four human (h) isoforms, hCA I, hCA II, hCA IV and hCA XII. Most of the synthesized compounds showed excellent in vitro carbonic anhydrase inhibitory properties comparable to those of the clinically used drug acetazolamide (AAZ). The new unprotected dipeptide-sulfonamide conjugates showed very effective inhibitory activity, in the low nanomolar range against II and XII, being less effective as hCA I and IV inhibitors. Four of the thirty compounds also showed strong inhibitory activity against hCA XII compared to AAZ.