Synthesis and carbonic anhydrase inhibitory activities of new thienyl-substituted pyrazoline benzenesulfonamides.

A series of new thienyl-substituted pyrazoline benzenesulfonamides were synthesized and their carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activities were tested on the human (h) isoforms hCA I and hCA II. The inhibition constant (Ki) of these sulfonamides were in the range of 232.16-637.70 nM toward the slow cytosolic isozyme hCA I, and in the range of 342.07-455.80 nM toward hCA II. Many of these compounds showed comparable inhibition with the reference sulfonamide acetazolamide, a clinically used drug. As the sulfonamide CA inhibitors (CAIs) show many therapeutic uses, these derivatives represent interesting examples of a novel class of such derivatives

Effects of low molecular weight plasma inhibitors of rainbow trout (Oncorhynchus mykiss) on human erythrocyte carbonic anhydrase-II isozyme activity in vitro and rat erythrocytes in vivo

The effects of low molecular weight plasma inhibitors from rainbow trout (Oncorhynchus mykiss) (RT) were investigated on the carbonic anhydrase enzyme (CA) activities in in vitro human and in in vivo Sprague–Dawley rat erythrocytes. The RT blood was used as extracellular fluid (plasma) source and plasma inhibitors were obtained by dialysis of the plasma. For the in vitro study, human carbonic anhydrase-II (HCA-II) isozyme was obtained by Sepharose 4B-l-tyrosine-sulfanylamide affinity chromatography with an overall purification of about 646-fold. The enzyme (specific activity of 7750 EU/mg protein) was obtained with a yield of 71.1% and SDS-PAGE showed a single band. From in vitro studies, the I50 value for RT plasma inhibitors obtained was 0.37 mg/ml. From in vivo studies on rat erythrocytes, CA activity was significantly inhibited by the inhibitors from the extracellular fluid of RT for up to 3 h (p<0.05) following intraperitoneal administration

Carbonic anhydrase inhibitory properties of novel sulfonamide derivatives of aminoindanes and aminotetralins.

We are greatly indebted to The Scientific and Technological Research Council of Turkey (TUBITAK, Grant no. TBAG-109T241) and Ataturk University (BAP2012/152) for their financial support of this study for (YA, AA, SG)

The effect of caffeic acid phenethyl ester (CAPE) on metabolic enzymes including acetylcholinesterase, butyrylcholinesterase, glutathione S-transferase, lactoperoxidase, and carbonic anhydrase isoenzymes I, II, IX, and XII.

This work was financed in part by two EU projects of the 7th FP, Metoxia and Dynano. Also, IG and SE would like to extend his sincere appreciation to the Research Chairs Program at King Saud University for providing funding to this research

Secondary sulfonamides as effective lactoperoxidase inhibitors

Secondary sulfonamides (4a–8h) incorporating acetoxybenzamide, triacetoxybenzamide, hydroxybenzamide, and trihydroxybenzamide and possessing thiazole, pyrimidine, pyridine, isoxazole and thiadiazole groups were synthesized. Lactoperoxidase (LPO, E.C.1.11.1.7), as a natural antibacterial agent, is a peroxidase enzyme secreted from salivary, mammary, and other mucosal glands. In the present study, the in vitro inhibitory effects of some secondary sulfonamide derivatives (4a–8h) were examined against LPO. The obtained results reveal that secondary sulfonamide derivatives (4a–8h) are effective LPO inhibitors. The Ki values of secondary sulfonamide derivatives (4a–8h) were found in the range of 1.096 × 10−3 to 1203.83 µM against LPO. However, the most effective inhibition was found for N-(sulfathiazole)-3,4,5-triacetoxybenzamide (6a), with Ki values of 1.096 × 10−3 ± 0.471 × 10−3 µM as non-competitive inhibition

Rosmarinic acid inhibits some metabolic enzymes including glutathione S-transferase, lactoperoxidase, acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase isoenzymes

Rosmarinic acid (RA) is a natural polyphenol contained in many aromatic plants with promising biological activities. Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread and intensively studied metalloenzymes present in higher vertebrates. Acetylcholinesterase (AChE, E.C. 3.1.1.7) is intimately associated with the normal neurotransmission by catalysing the hydrolysis of acetylcholine to acetate and choline and acts in combination with butyrylcholinesterase (BChE) to remove acetylcholine from the synaptic cleft. Lactoperoxidase (LPO) is an enzyme involved in fighting pathogenic microorganisms, whereas glutathione S-transferases (GSTs) are dimeric proteins present both in prokaryotic and in eukaryotic organisms and involved in cellular detoxification mechanisms. In the present study, the inhibition effects of rosmarinic acid on tumour-associated carbonic anhydrase IX and XII isoenzymes, AChE, BChE, LPO and GST enzymes were evaluated. Rosmarinic acid inhibited these enzymes with K(i)s in the range between micromolar to picomolar. The best inhibitory effect of rosmarinic acid was observed against both AChE and BChE

Antioxidant and Antiradical Properties of Selected Flavonoids and Phenolic Compounds

Phenolic compounds and flavonoids are known by their antioxidant properties and one of the most important sources for humans is the diet. Due to the harmful effects of synthetic antioxidants such as BHA and BHT, natural novel antioxidants have become the focus of attention for protecting foods and beverages and reducing oxidative stress in vivo. In the current study, we investigated the total antioxidant, metal chelating, Fe3+ and Cu2+ reduction, and free radical scavenging activities of some phenolic and flavonoid compounds including malvin, oenin, ID-8, silychristin, callistephin, pelargonin, 3,4-dihydroxy-5-methoxybenzoic acid, 2,4,6-trihydroxybenzaldehyde, and arachidonoyl dopamine. The antioxidant properties of these compounds at different concentrations (10–30 μg/mL) were compared with those of reference antioxidants such as BHA, BHT, α-tocopherol, and trolox. Each substance showed dose-dependent antioxidant activity. Furthermore, oenin, malvin, arachidonoyl dopamine, callistephin, silychristin, and 3,4-dihydroxy-5-methoxybenzoic acid exhibited more effective antioxidant activity than that observed for the reference antioxidants. These results suggest that these novel compounds may function to protect foods and medicines and to reduce oxidative stress in vivo

Carbonic anhydrase inhibitory properties of phenolic sulfonamides derived from dopamine related compounds

The effects of some phenolic sulfonamides were determined on the cytosolic carbonic anhydrase isoenzyme I and II (hCA I and II). Both isoenzymes were purified separately from human erythrocytes, using the Sepharose-4B-l-tyrosine-sulfanilamide affinity column chromatography method. In continuation of the study, we identified the inhibitory effects of phenolic sulfonamides 1–4 on the esterase activity of hCA I, and II. The inhibitory effects of phenolic sulfonamides 1–4 were tested on human carbonic anhydrase isoenzymes hCA I, and II. Among the compounds 1–4, compound 1 was concluded to show the best inhibitory effects. According to our data, IC50 values of compound 1 were found as 3.55 and 2.94 μM for hCA I, and hCA II, respectively. On the other hand, Ki values of this compound were found as 0.827 and 0.745 μM for both isoenzymes, respectively