Purification and characterization of carbonic anhydrase from sheep kidney and effects of sulfonamides on enzyme activity

Synthesis and evaluation of sulfonamide-bearing thiazole as carbonic anhydrase isoforms hCA I and hCA II

“…Some isoforms are cytosolic (CA I, CA II, CA III, CA VII and CA XIII), two are mitochondrial (CA VA and CAVB), others are membrane bound (CA IV, CA IX, CA XII and CA XIV), and one is secreted in saliva (CA VI). It has been reported that the CA XV isoform is not expressed in humans or in other primates, but it is abundant in rodents and other vertebrates 14,15 . These enzymes catalyze a very simple but critically important physiological reaction, rapid interconversion of carbon dioxide and water into protons and bicarbonate ions, in many physiological/pathological processes open up widespread opportunities for the development of diverse, specific inhibitors for clinical applications 16,17 .…”

Kinetic andin silicoanalysis of thiazolidin-based inhibitors of α-carbonic anhydrase isoenzymes

“…AZA and ZNA are also medium inhibitors with this assay and substrate against hCA I (K I -s of 14.8 and 36.2 µM, respectively). Kinetic investigations (Lineweaver Burk plots, data not shown) indicate that similarly to phenolic compounds, sulfonamides and inorganic anions 17,[26][27][28][29][30][31][32][33][34][35] , all the investigated compounds act as non-competitive inhibitors with 4-NPA as substrate, i.e. they bind in different regions of the active site cavity as compared to the substrate.…”

“…The best hCA II inhibitor in this series of derivatives was the bulky 6b (Figure 4), which with a K I of 0.81 µM, is similar inhibitor ZNA and AZA, a clinically used sulfonamide. It must be stressed that K I -s measured with the esterase method are most of the time in the micromolar range because hCA I and II are weak esterases [26][27][28][29][30][31][32][33][34] .…”

Carbonic anhydrase inhibitors: Design, synthesis and structural characterization of new heteroaryl-N-carbonylbenzenesulfonamides targeting druggable human carbonic anhydrase isoforms

“…[9] hCA VII presents a limited distribution, being mainly expressed in the cortex, hippocampus and thalamus regions within the mammalian brain where it is considered involved in generating neuronal excitation and seizures [4,10] as well as in neuropathic pain control. [11]. hCA IX is expressed in a limited number of normal tissues whereas it is overexpressed in many solid tumors and considered involved in critical processes connected with cancer progression.…”