In vitro investigation of the effect of 7,8-dihydroxyflavone on human carbonic anhydrase I and II isoenzymes

Carbonic anhydrase (CA) is a metalloenzyme that provides hydration of carbon dioxide. Of the 16 isoenzymes discovered in mammals, 15 of the CAs are also found in humans. Human carbonic anhydrase I (hCAI) and II (hCAII) are known as erythrocyte isoenzymes. These two isoenzymes are also involved in the regulation of blood pH, fluid electrolyte balance, respiration and digestion. Sulfonamide class drugs, especially acetazolamide (AZM), are CA inhibitors and are used for the treatment of glaucoma. The search for isoenzyme-selective inhibitors and activators for CAs continues. Phenolic compounds found in plants have a very rich class. They can show effects such as antioxidant, antidiarrheal, antiallergic, antimicrobial, antispasmodic, antiviral, antithrombosis and antihypertensive. 7,8-Dihydroxyflavone (7,8-DHF) is a member of the flavonoid subclass of phenolic compounds. This compound is an agonist of Tropomyosin receptor kinase B. Its effect on CA has not been investigated previously. In this thesis, we investigated the in vitro effects of 7,8-DHF on hCAI and hCAII isoenzymes using the esterase activity method. AZM was used as a positive control. Solutions of 7,8-DHF, which has low water solubility, were prepared in 17% DMSO (Dimethyl sulfoxide) at different concentrations between 0-3 mM. Among the concentrations indicated for 7,8-DHF, no inhibition of hCAI and hCAII isoenzymes of 50% or less was observed. Therefore, IC50 values for hCAI and hCAII of 7,8-dihydroxyflavone were not calculated. It showed inhibition of 14.1% and 14.7% for hCAI and hCAII isoenzymes, respectively, at a maximum concentration of 7.8-DHF of 3 mM. As a result, 7,8-DHF had no significant inhibition effect on the esterase activity of hCAI and hCAII isoenzymes.