Investigation of the effects of novel synthesized schiff base metal complexes on carbonic anhydrase enzyme activity by in vitro and In Silico methods

Aim: Enzymes are complex biomolecules, the majority of which are in protein structure, and have a wide range of uses in many sectors such as agriculture, medicine, food and industry. Their ability to be isolated from plant, animal and microorganism sources in practical and economical ways increases their application areas. Determining the inhibition mechanisms of these biomolecules in biological systems offers a unique control mechanism in the treatment of diseases and drug development studies. In this direction, within the scope of the thesis, the inhibition effects of newly synthesized Schiff base metal complexes on human carbonic anhydrase (hCA) I and II isoenzymes were investigated by in vitro and in silico methods. Material and Method: In our thesis study carried out for this purpose, hCA I and hCA II isoenzymes located in the erythrocyte cytosol were purified with the help of Sepharose-4B-L-Tyrosine-sulfonamide affinity column chromatography using human blood tissue. The inhibition effects of newly synthesized Schiff base metal complexes on the enzyme activity of each of these purified enzymes were investigated. Acetazolamide was used as the reference substance. Both IC50 and KI values were calculated for each metal complex and inhibition types were determined. Additionally, the effects of these substances on enzyme activity were examined using in silico methods. Results: While the KI values of the synthesized Schiff base derivatives ranged between 42.14 ± 4.47 nM and 322.80 ±18.98 nM for hCA I, they ranged from 33.37 ± 3.84 nM to 161.50 ±15.87 nM for hCA II. Result: It has been determined that the newly synthesized Schiff Base derivative compounds we used in the study inhibit hCA I and hCA II isoenzymes at significant levels. 2024, 51 Pages Keywords: Carbonic Anhydrase, Inhibition, Schiff Base.