Mechanisms of effect of indole derivative schiff base some compounds on human carbonic anhydrase isoenzymes and acetylcholinesterase enzyme

Introduction and Aim: Enzymes are biological catalysts that serve in all biochemical reactions that make up the metabolism in living systems. Carbonic anhydrase (E.C.4.2.1.1) was obtained from human erythrocytes, while acetylcholine esterase (AChE, acetylcholine acetylhydrolase, EC 3.1.1.7) was readily obtained. As the first step of the study, its in vitro effects on carbonic anhydrase isoenzyme I and II (hCA-I and hCA-II) were investigated. Material and Method: First, hCA-I and hCA-II isoenzymes were purified using Sepharose-4B-L-Tyrosine-sulfinamide affinity column chromatography. To determine the purity of the enzymes, SDS-PAGE was performed. After purification, the inhibition effects of indole derivative Schiff base compounds on hCA-I and hCA-II enzoenzymes were examined and Ki and IC50 values were calculated. In our study, the inhibitory effects of indole-derived schiff base compounds on AChE activity were also investigated. In the inhibition studies of AChE, activity was measured according to the Ellman method. IC50 and Ki values were calculated for each substance. Results: In the study, IC50 and Ki values were determined to be in the range of 38.50-231.05 nM and 36.18 ± 3.07-224.29 ± 5.78 nM for hCA-I isoenzyme, respectively. The same parameters were calculated in the range of 33.01-216.28 nM and 31.30 ± 2.63-201.64 ± 7.25 nM for the hCA-II isoenzyme. The IC50 and Ki values for AChE of indole derivative Schiff base compounds were determined to be in the range of 31.84 - 135.90 nM and 6.82 ± 0.72 - 110.30 ± 9.26 nM. Conclusions: It was observed that indole derivative Schiff base compounds inhibited hCA-I, hCA-II and AChE enzymes significantly.