Carbonic anhydrase inhibitors: in vitro inhibition of alpha isoforms (hCA I, hCA II, bCA III, hCA IV) by flavonoids

Ekinci D., Karagoz L., EKİNCİ D., ŞENTÜRK M., Supuran C. T.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, cilt.28, sa.2, ss.283-288, 2013 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 28 Sayı: 2
  • Basım Tarihi: 2013
  • Doi Numarası: 10.3109/14756366.2011.643303
  • Dergi Adı: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.283-288
  • Anahtar Kelimeler: Carbonic anhydrase, flavonoid, inhibitor, phenol, ACTIVE-SITE, PURIFICATION, COUMARINS, ISOZYMES, BINDING
  • Ondokuz Mayıs Üniversitesi Adresli: Evet

Özet

A series of flavonoids, such as quercetin, catechin, apigenin, luteolin, morin, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA). The compounds were tested against four alpha-CA isozymes purified from human and bovine (hCA I, hCA II, bCA III, hCA IV) tissues. The four isozymes showed quite diverse inhibition profiles with these compounds. The flavonoids inhibited hCA I with K-I-s in the range of 2.2-12.8 mu M, hCA II with K-I-s in the range of 0.74-6.2 mu M, bCA III with K-I-s in the range of 2.2-21.3 mu M, and hCA IV with inhibition constants in the range of 4.4-15.7, with an esterase assay using 4-nitrophenyl acetate as substrate. Some simple phenols/sulfonamides were also investigated as standard inhibitors. The flavonoids incorporate phenol moieties which inhibit these CAs through a diverse, not yet determined inhibition mechanism, compared to classic inhibitors such as the sulfonamide/sulfamate ones.