No abstract

Cardiovascular diseases are the leading cause of mortality worldwide. In recent years, the relationship between carbonic anhydrase inhibitors and atherosclerosis has attracted attention. In this study, we aimed to determine the in vitro effects of 35 frequently used cardiac drugs on human carbonic anhydrase I (hCA I) and II (hCA II). The inhibitory effects of the drugs on hCA I and hCA II were determined with both the hydratase and esterase methods. The most potent inhibitors observed were propafenone (hCA I: 2.8 µM and hCA II: 3.02 µM) and captopril (hCA I: 1.58 µM and hCA II: 6.25 µM). Isosorbide mononitrate, propranolol, furosemide, and atorvastatin were also potent inhibitors. The inhibitor constant, K i , value from the Lineweaver–Burk plot for propafenone was 2.38 µM for hCA I and 2.97 µM for hCA II. The tested cardiac drugs showed potent in vitro inhibition of the hCA I and II isozymes. Especially, in patients with atherosclerotic heart disease, these drugs may be preferred primarily due to the beneficial effects of carbonic anhydrase inhibition on atherosclerosis.

The investigation of carbonic anhydrase and paraoxonase enzyme inhibition properties of water-soluble zinc and gallium phthalocyanine complexes (1 and 2) are reported for the first time. The binding of p-sulfonylphenoxy moieties to the phthalocyanine structure favours excellent solubilities in water, as well as providing inhibition effect on carbonic anhydrase (CA) I and II isoenzymes and paraoxonase (PON1) enzyme. According to biological activity results, both complexes inhibited hCA I, hCA II and PON1. Whereas 1 and 2 showed moderate hCA I and hCA II (off-target cytosolic isoforms) inhibitory activity (Ki values of 26.09 µM and 43.11 µM for hCA I and 30.95 µM and 33.19 µM for hCA II, respectively), they exhibited strong PON1 (associated with high-density lipoprotein (HDL)) inhibitory activity (Ki values of 0.37 µM and 0.27 µM, respectively). The inhibition kinetics was analyzed by Lineweaver-Burk double reciprocal plots. It revealed that 1 and 2 were non-competitive inhibitors against PON1, hCA I and hCA II. These complexes can be advantageous than other synthetic CA and PON inhibitors due to their water solubility. Docking studies were carried out to examine the interactions between hCA I, hCA II and PON1 inhibitors and metal complexes at molecular level and to predict binding energies.

This study reports the facile synthesis of a novel series of benzothiazole‐chalcones, in addition to their inhibitory profile on important metabolic enzymes including human carbonic anhydrases (hCA‐I, hCA‐II) and paraoxonase (PON‐1). The inhibition parameters, IC50 (concentration for 50% inhibition) and Ki (dissociation constant) values, toward the title enzymes were determined for the studied compounds. As a result, IC50 values of hydratase activity were in the range 4.15–5.47 and 2.56–4.58 μM for hCA‐I and hCA‐II, respectively. At the same time, IC50 values of esterase activity were in the range 24.91–104.00 and 35.25–97.00 μM, while Ki values were in the range 14.43–59.66 and 26.65–73.34 μM for hCA‐I and hCA‐II, respectively. In addition, PON‐1 enzyme inhibition results showed interesting inhibitory effects, with IC50 values between 13.28 and 16.68 μM. Finally, a comprehensive approach was established for the synthesized compounds based on theoretical calculations, which have been done using B3LYP, PBE0 theories and SVP, TVZP, TVZPP basis sets, followed by docking studies by which the outputs proved the harmonically flows with the experimental results.

A series of 1-substituted-1H-benzimidazolium p-toluenesulfonate salts were synthesized in good yields by the reaction of 1-substituted benzimidazole derivatives and p-toluenesulfonic acid under microwave irradiation. Two iodide salts were synthesized by the anion exchange reaction of the corresponding p-toluenesulfonate salt and NaI.All compounds were characterized by 1 H NMR, 13 C NMR, IR, LC-MS spectroscopic methods, and elemental analyses. The crystal structure of 1-methoxyethyl-1Hbenzimidazolium p-toluenesulfonate 2d showed that cation and anion are interconnected by N−H···O and C−H···O hydrogen bonds. All compounds were examined as inhibitor of human carbonic anhydrase (hCA) I and II, and all of them inhibited hCA I and hCA II. Kinetic investigation results revealed that these compounds inhibit hCA I and hCA II in a non-competitive manner. The iodide salts had higher inhibitory activity than their corresponding p-toluenesulfonate salts.