The effect of coordination compounds on carbonic anhydrase (CA) activity

Abstract

Inhibition properties of some coordination compounds containing dicyanidogylene were investigated on human carbonic anhydrase I (CA I, E.C. 4.2.1.1). Carbonic anhydrase, a multifunctional enzyme, catalyzes reversibly a crucial reaction between carbon dioxide and water, leading to the formation of protons (H+) and bicarbonate (HCO3). CA inhibitors (CAIs) have clinical importance because they are used in the treatment of various diseases such as antiglaucoma, anticonvulsant and diuretics. Coordination complexes have remarkable biological activities such as antibacterial, antifungal and antitumor activities, and as therapeutic compounds due to their pharmaceutical properties. Metal complexes have effects on the inhibition of enzymes that play a role in biochemical reactions, which are important reactions for human life quality. In the present study, we investigate inhibitory effect of two coordination compounds ([Ni(bishydeten)2Ag(CN)2][Ag(CN)2].H2O and [Ni(edbea)Ag3(CN)5]) synthesized by our project team on hCA I and enzyme activity was measured by spectrophotometrically. Inhibition constant (Ki) were calculated from drawn Lineweaver Burk charts. These complexes exhibited effectively inhibitory effects on hCA I and Ki values were found as 635.30 nM and 184.01 nM, respectively. The IC50 values of the complexes against hCA I were 350.01 µM and 466.02 µM, respectively. Inhibition type of the complexes is noncompetitive against to hCA I enzyme activity. In conclusion, it has been indicated that novel coordination complexes have in vitro inhibitory effect on hCA. In the future, the inhibitory effect of these compounds can be observed in animal experiments for beneficial health effects and these data may lead to designing potent novel inhibitors.