Theoretical thermodynamic study on inhibition mechanism of α-human carbonic anhydrase enzyme by new class of benzenesulfonamides inhibitors

Theoretical thermodynamic study on inhibition mechanism of α-human carbonic anhydrase enzyme by new class of benzenesulfonamides inhibitors

In the present research, the inhibition power of benzenesulfonamides and their urea-derivatives compared to the acetazolamide as the reference drug in inhibition of the carbonic anhydrase enzyme model, isoform (IX), has been investigated using quantum mechanical calculations. All quantum calculations have been performed using density functional theory (DFT) using B3LYP model and 6-311+G** basis set at 298.15 K temperature and 1 atm pressure. In the first step, all four studied inhibitors were optimized in both gas and solvent phase using PCM method and then in order to investigate the effect of the inhibition power to inhibit the carbonic anhydrase enzyme, the anionic form of the inhibitors were constructed to interact with the active site of the enzyme model to create the enzyme-inhibitor complex. In the next step, all thermodynamic functions such as deprotonation enthalpy of inhibitors (∆HDP), Gibbs free energy (∆Grxn), standard entropy of reaction (∆Srxn) and reaction enthalpy (∆Hrxn) were calculated. According to the calculated results, the values of ∆Grxn and ∆Hrxn are negative for all four studied complexes and therefore the total reaction is exothermic and spontaneously.