Carbonic anhydrase inhibitors: guaiacol and catechol derivatives effectively inhibit certain human carbonic anhydrase isoenzymes (hCA I, II, IX and XII)

Scozzafava A., Passaponti M., SUPURAN C. T., GÜLÇİN İ.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, cilt.30, sa.4, ss.586-591, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 30 Sayı: 4
  • Basım Tarihi: 2015
  • Doi Numarası: 10.3109/14756366.2014.956310
  • Dergi Adı: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.586-591
  • Anahtar Kelimeler: Carbonic anhydrases, catechol derivatives, enzyme inhibition, guaiacol derivatives, isoenzymes, ERYTHROCYTE ISOZYMES I, ANTIOXIDANT ACTIVITY, VITRO ANTIOXIDANT, ISOFORMS I, THERAPEUTIC APPLICATIONS, SULFONAMIDE DERIVATIVES, ANTIRADICAL ACTIVITIES, CAFFEIC ACID, BIO-OIL, PHENOLS
  • Atatürk Üniversitesi Adresli: Evet

Özet

Carbonic anhydrases (CAs) are widespread metalloenzymes in higher vertebrates including humans. A series of phenolic compounds, including guaiacol, 4-methylguaiacol, 4-propylguaiacol, eugenol, isoeugenol, vanillin, syringaldehyde, catechol, 3-methyl catechol, 4-methyl catechol and 3-methoxy catechol were investigated for their inhibition of all the catalytically active mammalian isozymes of the Zn2+-containing CA (EC 4.2.1.1). All the phenolic compounds effectively inhibited human carbonic anhydrase isoenzymes (hCA I, II, IX and XII), with K(i)s in the range of 2.20-515.98 mu M. The various isozymes showed diverse inhibition profiles. Among the tested phenolic derivatives, compounds 4-methyl catechol and 3-methoxy catechol showed potent activity as inhibitors of the tumour-associated transmembrane isoforms (hCA IX and XII) in the submicromolar range, with high selectivity. The results obtained from this research may lead to the design of more effective carbonic anhydrase isoenzyme inhibitors (CAIs) based on such phenolic compound scaffolds.