Effects of some angiotensin converting enzyme-inhibitor drugs used for heart diseases on esterase activity of human carbonic anhydrase I and II

Effect of ACE-inhibitor drugs (Cilazapril, Perindopril, Ramipril, Trandolapril, and Zofenopril calcium) used for heart diseases were investigated in vitro on esterase activity of human carbonic anhydrase I and II (hCA-I and hCA-II) purified from human erythrocytes by using Sepharose-4B-L-tyrosine-sulfanilamide affinity gel. hCA-I was purified 94.62 fold with a specific activity of 704.35 EU/mg protein and 67.5 % yield, hCA-II was purified 470.19 fold with a specific activity of 3500 EU/mg protein and 54.69% yield. Afterwards purity of isozymes was controlled by SDS-PAGE. In order to determine the effect of these drugs, absorbances were determined at 348 nm by hydrolysis of p-nitrophenylacetate which is the substrate. IC50 values were calculated by drawing % Activity-[Inhibitor] graphs. IC50 values of these drugs were between 0.090 -0.226 µM for hCA-I esterase activity and between 0.195 -0.201 µM for hCA-II esterase activity. All of these drugs showed inhibition effect on both hCA-I and hCA-II. Trandolapril and Perindopril showed the best inhibition effect on hCA-I and hCA-II, respectively. Molecular docking studies were used in order to understand the interaction of these drugs with the domains of hCA-I and hCA-II. All of these drugs interact with amino acids in the binding pocket of hCA-I and hCA-II except Zofenopril calcium in case of hCA-II interacts with H2O in the active site. In the light of the results, it can be concluded that in vivo investigation of these drugs on carbonic anhydrase may be important. These drugs may be lead to increase tissue CO2 concentrations and lower tissue pH, resulting in vascular dilation and increased blood flow, which means that the patient could be suffering from the onset of a new disease during using these drugs.