Results in Chemistry (Dec 2023)
Molecular docking and inhibition profiles of some antidepressants on human carbonic anhydrase enzymes
Abstract
Inhibition of human carbonic anhydrase (hCA) enzymes is a bright target since these isoenzymes take part in various physiological events and inhibitors of these enzymes are potent drug candidates for several diseases. In this study, we investigated the influences of commonly used antidepressants, risperidone, mirtazapine and sodium valproate on hCA I and II and deter-mined their kinetics. Antidepressant compounds showed Ki values ranging from 0.0054 to 222.5 µM against hCA I, 0.0004 to 392.9 µM against hCA II. According to the molecular docking study, risperidone and mirtazapine which are the most active inhibitors have the glide scores with 6.568 kcal/mol and −7.385 kcal/mol against hCA I and hCA II enzymes, respectively. The binding analysis of the inhibitor-enzyme complexes has revealed that their inhibition mechanisms result from interactions with the critical residue of the catalytic active site or Zn atom. Our finding shows that antidepressants have crucial inhibition effects on CA enzymes and that risperidone was found to be much more effective than acetazolamide, a standard clinically used inhibitor of carbonic anhydrase. As inhibitors of CA enzymes are important drug candidates for various diseases, risperidone is a promising compound which needs to be further investigated to produce novel derivatives.
