QM Study on the Mechanism of Carbonic Anhydrase XII Inhibition with Glycosyl Coumarin as Non-Zinc Mediated Inhibitors

Metalloenzyme carbonic anhydrases (CAs, EC 4.2.1.1) present in prokaryotes and eukaryotes which is encoded by three distinct gen families: (i) α-CA, (ii) β-CA and (iii) γ-CAs. In recent years a novel group of inhibitors of CA that belong to the new chemotype molecules including coumarins and their derivatives have been reported [1, 2]. In this research, inhibition mechanism of zinc enzyme carbonic anhydrase XII (CA XII) by a novel class of suicide inhibitors, glycosyl coumarin, has been modeled using of density functional theory DFT at the B3LYP level using 6-31+G* basis set to study the electronic structures and thermocemical aspects of this mechanism. In the first step of this research the most stable conformer of 7-substituted sugar coumarin, melibiose coumarin as more effective and coumarin as the less effective inhibitor of CA XII respectively has been search and interact with CA XII active site. The results of calculations indicate that mentioned inhibitor do not directly interact with the metal ion from the CA active center. Moreover, the calculated thermodynamic function values indicate the presence of sugar moiety in the coumarin molecule was associated with more effective inhibition [3, 4]. In addition the good agreements between the calculated results with experimental data indicate a reliable agreement of method of calculations.