The specific inhibition effects of benzothiazole sulfonamide derivatives on tumor-associated carbonic anhydrase IX, XII (CA-IX, CA-XII) isoenzymes and cytosolic carbonic anhydrase I, II (CA-I, CA-II) isoenzymes

Carbonic anhydrases (CAs, EC 4.2.1.1) involved in respiration and transport of CO2/bicarbonate between metabolizing tissues and lungs, pH and CO2 homeostasis, electrolyte secretion in various tissues, biosynthetic reactions (gluconeogenesis, lipogenesis, ureagenesis etc.), bone resorption, calcification, tumorigenicity and many other physiologic or pathologic processes. CA-I and CAII are two major cytosolic CA isoenzymes that found in mammalian red blood cells. CA-IX and CA-XII are tumor associated isoenzymes which have contribution to tumor development by stimulating extracellular acidification. This study deals with inhibition effects of new synthesized benzothiazole sulfonamide derivatives on CA-I, CA-II, CA-IX and CA-XII. All inhibition studies were performed with SX.18MV-R Applied Photophysics Stopped-Flow Kinetic Instrument. According to the findings of the study, AnA14 is the most potent inhibitor for CA-I and CA-II with the inhibition values 8,11 and 0,19 μM, respectively. The other benzothiazole sulfonamide derivatives have great inhibition effects for CA-IX and CA-XII isoenzymes.