Sulfonamide derivatives with benzothiazole scaffold: Synthesis and carbonic anhydrase I-II inhibition properties.

The secondary sulfonamide derivatives containing benzothiazole scaffold (1-10) were synthesized to determine their inhibition properties on two physiologically essential human carbonic anhydrases isoforms (hCAs, EC, 4.2.1.1), hCA I, and hCA II. The inhibitory effects of the compounds on hCA I and hCA II isoenzymes were investigated by comparing their IC50 and Ki values. The Ki values of compounds (1-10) against hCA I and hCA II are in the range of 0.052 ± 0.022-0.971 ± 0.280 and 0.025 ± 0.010-0.682 ± 0.335, respectively. Some of these inhibited the enzyme more effectively than the standard drug, acetazolamide. In particular, compounds 5 and 4 were found to be most effective on hCA I and hCA II.

Piperazine derivatives with potent drug moiety as efficient acetylcholinesterase, butyrylcholinesterase, and glutathione S-transferase inhibitors.

Cholinesterases catalyze the breakdown of the neurotransmitter acetylcholine (ACh), a naturally occurring neurotransmitter, into choline and acetic acid, allowing the nervous system to function properly. In the human body, cholinesterases come in two types, including acetylcholinesterase (AChE; E.C.3.1.1.7) and butyrylcholinesterase (BChE; E.C.3.1.1.8). Both cholinergic enzyme inhibitors are essential in the biochemical processes of the human body, notably in the brain. On the other hand, GSTs are found all across nature and are the principal Phase II detoxifying enzymes in eukaryotes and prokaryotes. Specific isozymes are identified as therapeutic targets because they are overexpressed in various malignancies and may have a role in the genesis of other diseases such as neurological disorders, multiple sclerosis, asthma, and especially cancer cell. Piperazine chemicals have a role in many biological processes and have fascinating pharmacological properties. As a result, therapeutically effective piperazine research is becoming more prominent. Half maximal inhibition concentrations (IC50 ) of piperazine derivatives were found in ranging of 4.59-6.48 µM for AChE, 4.85-8.35 µM for BChE, and 3.94-8.66 µM for GST. Also, piperazine derivatives exhibited Ki values of 8.04 ± 5.73-61.94 ± 54.56, 0.24 ± 0.03-32.14 ± 16.20, and 7.73 ± 1.13-22.97 ± 9.10 µM toward AChE, BChE, and GST, respectively. Consequently, the inhibitory properties of the AChE/BChE and GST enzymes have been compared to Tacrine (for AChE and BChE) and Etacrynic acid (for GST).

In vitro and in silico enzyme inhibition effects of some metal ions and compounds on glutathione S-transferase enzyme purified from Vaccinium arctostapylous L.

Glutathione s-transferase (GST) is a class of enzymes that performs a wide array of biological functions. However, GST enzymes are most famously known for their roles in catalyzing the conjugation of reduced glutathione (GSH) to electrophilic centers on a wide variety of substrates to induce water-solubility to compounds as a protective antioxidant mechanism against toxic substances. In the present study, in vitro inhibition effects of coumarin, ascorbic acid, sodium sulfide, sodium azide, citric acid compounds, and Cd2+, Cu2+, Ni2+, Mg2+ metal ions against GST enzyme were determined. For this aim, the GST enzyme was purified from Vaccinium arctostapylous L. using the glutathione-agarose affinity chromatography and Sephadex G-100 gel filtration steps. The respective metals and chemical compounds were used at different concentrations for measuring their in vitro GST activity effects. The Ki values of these agents were determined as 0.450 ± 0.13, 15.05 ± 7.05, 0.009 ± 0.001, 0.022 ± 0.006, 0.120 ± 0.36, 0.150 ± 0.06, 0.223 ± 0.03, 0.002 ± 0.0003, and 0.136 ± 0.06 mM, respectively. Finally, the molecular docking interactions of the compounds with the GST target enzyme were evaluated using Autodock Tools-1.5.6. The effective molecular interactions of coumarin, citric acid, ascorbic acid, and sodium sulfide with GST target enzyme were found with their binding lowest energy affinities -4.62, -3.04, -2.53, and -1.67 kcal/mol, respectively.Communicated by Ramaswamy H. Sarma.

Inhibition effects of some antidepressant drugs on pentose phosphate pathway enzymes.

The glucose metabolism in the pentose cycle is essential to the source of NADPH. Deficiency of these enzymes have been linked to depression and psychotic disorders. Depression is an increasingly prevalent mental disorder which may cause loss of labor. Antidepressant drugs are commonly employed in treatments of mood disorders and anxiety treatment. The purpose of this study is to investigate the effects of aripiprazole, mirtazapine, risperidone, escitalopram and haloperidol on the activity of 6-phosphogluconate dehydrogenase (6PGD) and glucose-6-phosphate dehydrogenase (G6PD) enzymes purified from human erythrocytes. It was found that aripiprazole, mirtazapine, risperidone, escitalopram and haloperidol show effective inhibitor properties on purified G6PD and 6PGD enzymes. The IC50 values of these drugs were found in the range of 26.34 µM-5.78 mM for 6PGD and 16.26 µM-3.85 mM for G6PD. The Ki values of the drugs were found in the range of 30.21 ± 4.31 µM-4.51 ± 1.83 mM for 6PGD and 14.12 ± 3.48 µM-4.98 ± 1.14 mM for G6PD. Usage of drugs with significant biological effects may be a hazard in some conditions.

Differential effects of selective serotonin reuptake inhibitors on paraoxonase-1 enzyme activity: An in vitro study.

Paraoxonase-I (PON1) is a calcium-dependent hydrolytic enzyme, plays an important role in most antioxidant properties related to high-density lipoprotein (HDL). Antidepressant drugs are commonly employed in treatment of mood disorders and anxiety treatment. In this study, human serum PON1 was purified using simple reproducible procedures and the effects of some antidepressant drugs on its activity were determined. It was found that mirtazapine, aripiprazole, escitalopram, and risperidone exhibited potential inhibitory properties on the purified PON1 activity with IC50 values in the range of 115.50-231.00 µM and Ki values in the range of 41.66 ±â€¯4.27 µM-276.36 ±â€¯35.28 µM. Both risperidone and escitalopram inhibited PON1 activity competitively, while both aripiprazole and mirtazapine inhibited PON1 activity non-competitively. Chlorpromazine did not affect PON1 activity. Usage of drugs with significant biological activity may be hazardous in some cases.

Purification and characterization of glutathione S-transferase from blueberry fruits (Vaccinium arctostaphylos L.) and investigated of some pesticide inhibition effects on enzyme activity.

Pesticides cause pollution by remaining in water, soil, fruits and vegetables for a long time and also reach human through the food chain. It was thought that some pesticides used in agriculture could adversely affect the antioxidant enzyme system and the minimum inhibition values were studied. glutathione s-transferase (GST), an important antioxidant enzyme, catalyzes the conjugation of glutathione with toxic metabolites. It was purified from the blueberry fruits. The purification of the enzyme was performed separately by affinity and gel filtration chromatography. The purity of the enzyme was determined by SDS-PAGE electrophoresis. Characterization studies were done for the enzyme. For this purpose, optimal pH, temperature, Km and Vmax values for GSH and CDNB were also determined for the enzyme as 7.2 in K-phosphate buffer, 50 °C, 1.0 M, 7.0 in K-phosphate buffer, 1.57 mM; 0.17 mM and 0.048 EU/mL, 0.0159 EU/mL, respectively. Additionally, inhibitory effects of some pesticides; dichlorvos, acetamiprid, cyhalothrin, haloxyfop-p-Methyl, 2,4 dichlorophenoxy acetic acid, cypermethrin, imidacloprid, fenoxaprop-p-ethyl, glyphosate isopropylamine salt were examined the enzyme activity in vitro by performing Lineweaver-Burk graphs and plotting activity % IC50 and Ki values were calculated for each of pesticides. All of the pesticides inhibited the GST enzyme at millimolar level. Pesticide showing the best inhibitory effect was found as dichlorvos. The Ki value which is the inhibition constant of this pesticide was 0.0175 ± 0.005.