The inhibition studies of 2-amino-6-methoxy benzothiazole and dipicolinic acid derivatives on carbonic anhydrase isoenzyme

THE INHIBITION STUDIES OF 2-AMINO-6-METHOXY BENZOTHIAZOLE AND DIPICOLINIC ACID DERIVATIVES ON CARBONIC ANHYDRASE Melike ASLAN Chemistry Department, MSc. Thesis, 2014 Thesis Supervisor: Assoc. Prof. Metin BÜLBÜL SUMMARY Carbonic anhydrase (E.C. 4.2.1.1) is a metalloenzyme and contains zinc(II) ion in its active side. It catalyses the reversible reaction of CO2 to HCO3- and H+ ions. In this study, the inibition effects of new carbonic anhydrase (CA) inhibitors's, which candidates for treatment of glaucoma, or carbonic anhydrase enzyme have been investigated. Firstly, erythrocyte carbonic anhydrase isoenzymes (CA-I, CA-II) from human erythrocyts were separately purifed by affinity chromatography. Electrophoresis and specific activity was proven by the determination of impurities. Later, the inhibition effects of newly synthesized compounds (1-6) on CA-I and CA-II isoenzymes were determined. To determine inhibitory effects of the compounds, the hydratase and esterase activities of carbonic anhydrase enzyme were measured. %Activity vs. [I] graphics were drawn and the IC50 values were calculated for potential inhibitory compounds. According to in vitro studies, any inhibition effects of 1-6 compounds were not observed on hydratase activity of CA-I and CA-II isoenzymes. These new compounds inhibited the esterase activities of CA-I and CA-II isoenzymes. The IC50 values of compounds for esterase activity are 0,800 – 0,193 mM for CA-I and 0,754 – 0,174 mM for CA-II, respectively. Keywords: IC50 Values, Inhibition, Carbonic Anhydrase, Benzothiazole, Dipicolinic acid.