Carbonic anhydrase inhibitors. Inhibition of red blood cell ostrich (Struthio camelus) carbonic anhydrase with a series of aromatic and heterocyclic sulfonamides

Abstract

The purification of red blood cell carbonic anhydrase (CA, EC 4.2.1.1) from ostrich (scCA) blood is reported, as well as an inhibition study of this enzyme with a series of aromatic and heterocylic sulfonamides. The ostrich enzyme showed a high activity, comparable to that of the human isozyme II, with k_cat of 1.2·10⁶ s^{− 1} and k_cat/K_M of 1.8·10⁷ M^{− 1} s^{− 1}, and an inhibition profile quite different from that of the human red blood cell cytosolic isozymes hCA I and II. scCA has generally a lower affinity for sulfonamide inhibitors as compared to hCA I and II. The only sulfonamide which behaved as a very potent inhibitor of this enzyme was ethoxzolamide (K_I = 3.9 nM) whereas acetazolamide and sulfanilamide behaved as weaker inhibitors (inhibition constants in the range 303–570 nM). Several other aromatic and heterocyclic sulfonamides, mostly derivatives of sulfanilamide, homosulfanilamide, 4-aminoethylbenzenesulfonamide or 5-amino-1,3,4-thiadiazole-2-sulfonamide, showed good affinities for the ostrich enzyme, with K_I values in the range 25–72 nM.

Keywords::

• Carbonic anhydrase
• sulfonamide
• ostrich
• inhibitor
• enzyme inhibition

Acknowledgements

During the course of this study, the Scientific and Technical Research Council of Turkey (TUBITAK) provided a scholarship (NATO-A2) to Ozen Ozensoy, which is gratefully acknowledged. The authors also thank Balikesir University, Research Center of Applied Sciences (BURCAS/Balikesir, Turkey) for providing the research facilities.