The synthesis of (Z)-4-oxo-4-(arylamino)but-2-enoic acids derivatives and determination of their inhibition properties against human carbonic anhydrase I and II isoenzymes

OKTAY K., KOSE L. P., Sendil K., GÜLTEKİN M. S., GÜLÇİN İ., SUPURAN C. T.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, cilt.31, sa.6, ss.939-945, 2016 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 31 Sayı: 6
  • Basım Tarihi: 2016
  • Doi Numarası: 10.3109/14756366.2015.1071808
  • Dergi Adı: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.939-945
  • Anahtar Kelimeler: Butenoic acid, carbonic anhydrase, enzyme inhibition, enzyme purification, isoenzymes, TROUT ONCORHYNCHUS-MYKISS, ACETYLCHOLINE ESTERASE INHIBITORS, ERYTHROCYTE ISOZYMES I, ENZYME-ACTIVITY, LACTOPEROXIDASE ENZYME, ANTIGLAUCOMA ACTION, PHENOLIC-COMPOUNDS, HCA I, VITRO, VIVO
  • Atatürk Üniversitesi Adresli: Evet

Özet

The synthesis of (Z)-4-oxo-4-(arylamino)but-2-enoic acid (4) derivatives containing structural characteristics that can be used for the synthesis of several active molecules, is presented. Some of the butenoic acid derivatives (4a, 4c, 4e, 4i, 4j, 4k) are synthesized following literature procedures and at the end of the reaction. In addition, structures of all synthesized derivatives (4a-4m) were determined by H-1-NMR, C-13-NMR and IR spectroscopy. Carbonic anhydrase is a metalloenzyme involved in many crucial physiologic processes as it catalyzes a simple but fundamental reaction, the reversible hydration of carbon dioxide to bicarbonate and protons. Significant results were obtained by evaluating the enzyme inhibitory activities of these derivatives against human carbonic anhydrase hCA I and II isoenzymes (hCA I and II). Butenoic acid derivatives (4a-4m) strongly inhibited hCA I and II with K(i)s in the low nanomolar range of 1.85 +/- 0.58 to 5.04 +/- 1.46 nM against hCA I and in the range of 2.01 +/- 0.52 to 2.94 +/- 1.31 nM against hCA II.