Synthesis and carbonic anhydrase I, II, IV and XII inhibitory properties of N-protected amino acid - sulfonamide conjugates

KÜÇÜKBAY F., Kucukbay H., TANC M., SUPURAN C. T.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, cilt.31, sa.6, ss.1476-1483, 2016 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 31 Sayı: 6
  • Basım Tarihi: 2016
  • Doi Numarası: 10.3109/14756366.2016.1147438
  • Dergi Adı: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1476-1483
  • Anahtar Kelimeler: Carbonic anhydrase, glaucoma, inhibitor, N-protected amino acid, sulfonamide, TARGETING TUMOR HYPOXIA, BIOCHEMICAL-CHARACTERIZATION, PORPHYROMONAS-GINGIVALIS, DRUG TARGETS, PATENT, DERIVATIVES, ISOENZYMES, COUMARINS, AGENTS, ALPHA
  • İnönü Üniversitesi Adresli: Evet

Özet

N-protected amino acids (Gly, Ala and Phe protected with Boc and Z groups) were reacted with sulfonamide derivatives, leading to the corresponding N-protected amino acid-sulfonamide conjugates. 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. Among them, hCA II, IV and XII are antiglaucoma drug targets, being involved in aqueous humor secretion within the eye. Low nanomolar inhibition was measured against all four isoforms with the 20 reported sulfonamides, but no selective inhibitory profiles, except for some CA XII-selective derivatives, were observed. hCA I, II and XII were generally better inhibited by sulfonamides incorporating longer scaffolds and Gly/Ala, whereas the best hCA IV inhibitors were homosulfanilamide derivatives, incorporating Phe moieties. The amino acid-sulfonamide conjugates show good water solubility and effective hCA II, IV and XII inhibition, and may be considered as interesting candidates for antiglaucoma studies.