Some Anti‐Inflammatory Agents Inhibit Esterase Activities of Human Carbonic Anhydrase Isoforms I and II: An In Vitro Study

Abstract

Carbonic anhydrases (CAs) are known as a drug-target enzymes. The inhibitors of the enzyme are important compounds for discovering new therapeutic agents and understanding in detail protein-drug interactions at the molecular level. For this purpose, the in vitro effects of some anti-inflammatory agents such as tenoxicam, fluorometholone acetate, and dexamethasone were investigated on esterase activity of human erythrocyte CA-I and CA-II in this study. hCA-I and hCA-II were purified by affinity chromatography with a yield of 47.25% and 87%, and a specific activity of 642.8 EU/mg proteins and 5576.9 EU/mg proteins, respectively. SDS-PAGE was performed to determine the purity of the enzymes. Inhibitory effects of the drugs on hCA-I and hCA-II were determined by spectrophotometric method. IC50 values for hCA-I and hCA-II were 0.198, 2.18, 11.7, 0.11, 17.5 and 14 μm using tenoxicam, fluorometholone acetate, and dexamethasone, respectively. For fluorometholone acetate and dexamethasone, Ki values from Lineweaver-Burk plots were obtained as 1.044 and 21.2 μm (noncompetitive) for hCA-I and 9.98 and 8.66 μm (non-competitive) for hCA-II. In conclusion, tenoxicam, fluorometholone acetate, and dexamethasone showed potent inhibitory effects on esterase activity of hCA-I and hCA-II isozymes under in vitro conditions.

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

“…Compound 5b behaved as a good inhibitor on hCA I and hCA II with an activation constant of 0.35 mM. Enzyme inhibition is a very important issue for drug design and biochemical applications [45][46][47][48] . The results put forward that new sulfonamide derivatives inhibited the hCA I and II enzyme activity.…”

Assessment of the inhibitory effects and molecular docking of some sulfonamides on human serum paraoxonase 1

“…Nowadays, drugs that function as enzyme inhibitors constitute a significant proportion of the currently used therapeutically active agents. Therefore, the investigation of the effects of medical active compounds on metabolic enzymes is very important for drug design studies . In this study, we examined the in vitro effects of some sulfonamide compounds on human serum PON1 activity.…”

Preparation of Two Maleic Acid Sulfonamide Salts and Their Copper(II) Complexes and Antiglaucoma Activity Studies

“…[1][2][3] Carbonic anhydrase (CA) is ubiquitous metalloenzyme that catalyze the two physiologically important processes: the first, the hydration of carbon dioxide to bicarbonate ion and a proton, and the second, the dehydration of bicarbonate ion. [4][5][6] These simple reactions provide acid-base equilibrium and ion equilibrium, so carbonic anhydrases are involved in many physiological processes such as pH regulation, ion transport, electrolyte secretion, calcification, and some biosynthetic reactions. 4,7 Among the mammalian carbonic anhydrases, α-carbonic anhydrases, sixteen different CA isoforms are expressed in humans.…”

“…4,7 Among the mammalian carbonic anhydrases, α-carbonic anhydrases, sixteen different CA isoforms are expressed in humans. 5,6 Human carbonic anhydrase (hCA) II isozyme which is present on the human eye 8 interacts with some membrane transport proteins, including chloride/bicarbonate exchanger, sodium/proton exchanger, and the sodium bicarbonate cotransporter. 9 Thus hCA II plays a key role in the production of aqueous humor.…”

“…[10][11][12] One of the methods used in glaucoma treatment is to reduce the production of aqueous humor 10,13 by using carbonic anhydrase inhibitors. 4,5,11,13,14 2-Aminopyridines and benzimidazoles serve as useful chelating ligands in a variety of inorganic and organometallic applications, [15][16][17] and also act as monodentate ligands which coordinate the metal ions through the nitrogen of the ring [16][17][18][19][20][21] in most cases. In addition, there are several works on 2-aminopyridine complexes in which the amino group also participates in coordination.…”