Secondary/tertiary benzenesulfonamides with inhibitory action against the cytosolic human carbonic anhydrase isoforms I and II


ALP C., MARESCA A., Alp N. A., GÜLTEKİN M. S., Ekinci D., SCOZZAFAVA A., ...Daha Fazla

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, cilt.28, sa.2, ss.294-298, 2013 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 28 Sayı: 2
  • Basım Tarihi: 2013
  • Doi Numarası: 10.3109/14756366.2012.658788
  • Dergi Adı: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.294-298
  • Anahtar Kelimeler: Carbonic anhydrase, benzenesulfonamide, tosyl, inhibitor, ISOZYME-I, THERAPEUTIC APPLICATIONS, COUMARINS, MECHANISM, SERIES
  • Atatürk Üniversitesi Adresli: Evet

Özet

Carbonic anhydrase inhibitors of primary sulfonamide type, RSO2NH2, have clinical applications as diuretics, antiglaucoma, antiepileptic, antiobesity and antitumor drugs. Here we investigated inhibition of two human cytosolic isozymes, hCA I and II, with a series of secondary/tertiary sulfonamides, incorporating tosyl moieties (CH(3)C(6)H(4)SO(2)NR1R2). Most compounds inhibited both isoforms in low micromolar range, with inhibition constants between 0.181-6.01 mu M against hCA I, and 0.209-0.779 mu M against hCA II, respectively. These findings point out that substituted benzenesulfonamides may be used as leads for generating interesting CAIs probably possessing a distinct mechanism of action compared to primary sulfonamides. Indeed, classical RSO2NH2 inhibitors bind in deprotonated form to the Zn(II) ion from the CA active site and participate in many other favorable interactions with amino acid residues lining the cavity. The secondary/tertiary sulfonamides cannot bind to the zinc due to steric hindrance and probably are accommodated at the entrance of the active site, in coumarin binding-site.