Investigation of the effect of bergamottin on the activity of carbonic anhydrase I and II isoenzymes

Carbonic Anhydrase (CA) enzymes play crucial roles in essential biological processes such as physiological pH balance, respiration, and electrolyte transport by catalyzing the hydration of carbon dioxide (CO2). Abnormal activity of CA isoenzymes has been associated with various pathologies such as cancer, obesity, and epilepsy, and research into the development of new inhibitors specific to these isoenzymes remains ongoing. In this thesis, the potential effects of bergamottin (BGM), a natural furanocoumarin derivative, on human carbonic anhydrase I (hCA I) and II (hCA II) isoenzymes were evaluated in vitro using esterase and hydrase activity assays; additionally, enzyme-ligand interactions were investigated via molecular docking analyses. For comparison, acetazolamide (AZM) and L-Histidine (HIS) were used as positive controls. The measurements conducted with various concentrations of BGM (ranging from 0 to 500 µM) showed a significant decrease in the activity of both enzyme isoforms. According to the esterase activity results, the IC50 values of BGM for hCA I and hCA II were calculated to be 742.5 µM and 49.09 µM, respectively. In the hydrase activity assay, an IC50 value of 140 µM was determined for hCA II, while no IC50 value could be calculated for hCA I despite the inhibitory effect being observed. Molecular docking analysis revealed that BGM showed high affinity for both CA I and CA II enzymes, with binding score of -7.6 kcal/mol and -8.2 kcal/mol, respectively. When the in vitro and in silico data were considered together, it was concluded that bergamottin could be a potential natural inhibitor capable of inhibiting the activity of both hCA I and II isoenzymes.