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The principle purpose of this study is to synthesize some Schiff base derivatives with a new microwave irradiation technique and investigate their enzyme inhibition effects. Related Schiff base compounds (1 a–1 h) were synthesized from 4‐fluoro aniline and some substituted benzaldehyde derivatives (3 a–3 h). The chemical structures of Schiff bases were elucidated by various spectroscopic methods (1H NMR, 13C NMR). The inhibitory effects of the synthesized compounds against acetylcholinesterase, butyrylcholinesterase and glutathione S‐transferase were investigated. The in vitro enzyme study determined the best enzyme inhibitors for AChE, BChE, and GST enzymes as 3 h, 3 b, and 3 e compounds, respectively. The results were compared with the standard drugs tacrine for cholinesterase and ethacrynic acid for GST enzymes. Molecular docking results demonstrated the low binding energy values between −5.8 kcal/mol and −8.7 kcal/mol with hydrogen bonding, hydrophilic, and hydrophobic interactions at the active catalytic sites of the enzymes. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Daucus carota L. ssp. major (DCM) plant is widely used in traditional medicine to treat some types of cancer and various diseases. Therefore, we evaluated the biological activities of this plant to define its effects against prostate cancer (PCa), Alzheimer's disease (AD), oxidation, and diabetes mellitus (DM) as well as identified its phenolic composition. To determine the anti‐cancer properties of the plant extract, we treated PCa cells with the extract at a concentration range of 0.25, 0.5, 1, 2, and 4 mg/ml. Significant results were obtained against the PC3 cells compared to normal PNT1a prostate epithelial cells. As a result of precise measurements at the millimolar level, it was observed that the plant extract showed an effective inhibition (IC50) against glutathione S‐transferase (GST; 12.84 mM), acetyl cholinesterase (AChE; 15.07 mM), and α‐Gly (11.75 mM) enzymes when compared with standard inhibitors. Antioxidant activities of DCM methanol extract were determined via two well‐known in vitro techniques. The extracts showed antioxidant activities against the DPPH and ABTS+. The LC‐ESI‐MS/MS was used to determine the phenolic compounds of methanol extract from DCM. Chlorogenic acid (2,089.096 µg/g), shikimic acid (193.14 µg/g), and coumarin (113.604 µg/g) were characterized as major phenolic compounds. In addition, the interactions of chlorogenic acid, chrysin, coumarin, and shikimic acid with the used three enzymes have been calculated using molecular docking simulation. Practical applications: Plant natural phenolic compounds have protective effects such as anti‐inflammatory, antioxidant, anticarcinogen, and enzyme inhibitory. Therefore, it has an important place in the food and pharmaceutical industry. The present study aims to reveal the enzyme inhibitory, antioxidant, and anticarcinogenic properties of the Daucus carota ssp. Major (DCM) plant extract. Significant results were obtained against the PC3 cells compared to normal PNT1a prostate epithelial cells. DCM extract demonstrated considerable antioxidant activity and inhibitory potential on used metabolic enzymes. These biological effects are thought to have a relationship with rich chemical composition. [ABSTRACT FROM AUTHOR]

Glutathione S-transferases are multifunctional enzymes for the cellular defense against xenobiotics and provide protection for organism. In this study, the inhibition effects of some antibiotics were investigated against GST obtained from albino-rats kidney, liver, and heart tissues. Ninety-six albino-rats were randomly divided into 16 groups (n:6). The first four groups were control groups that were administrated blank enjection and decapitated at 1–7 h. The other groups were administrated the antibiotics. In all tissues, GST activity was increased in antibiotics groups at 1st and 3rd hours compared to control groups, while it began to fall at 5th and 7th hours (p <.05). In kidney tissues, it was lower than the same control group the cefuroxime and cefoperazone groups at 7th hours (p <.05). In addition, almost all antibiotic groups of kidney tissues had higher GST activity at all hours than those of control groups, but it was higher only at 5th hours in heart tissues (p <.05). [ABSTRACT FROM AUTHOR]

Glutathione S-transferase (GST) enzymes detoxify a broad spectrum of xenobiotics, including chemotherapeutic drugs, environmental carcinogens, and endogenous molecules. Glutathione transferases catalyze the conversion of some metabolites into less toxic substances. Phase II reactions, which often result in detoxification, are conjugation reactions of glutathione through GST enzymes that protect the organism from the attacks of highly reactive electrophilic substances. Since the GST enzyme can metabolize toxic exogenous compounds, it has been extensively investigated in mammals. In this study, the GST enzyme was purified in human erythrocytes with a specific activity of 5.56 EU mg-1 protein and a yield of 2316.0 fold with 65% efficienc. SDS-polyacrylamide gel electrophoresis was performed to check the purity of the purified enzyme and the molecular mass was determined to be about 26 kDa. The IC50 and Ki values for amoxycillin and vancomycin hydrochloride drugs on the purified GST enzyme were calculated and the type of inhibition was determined. As a result of the inhibition studies, we observed that these antibiotics inhibited the GST enzyme at low doses. [ABSTRACT FROM AUTHOR]

• New 1,2,3-triazole derivatives containing chalcone (1–7) were synthesized. • All newly compounds were characterized by IR, 1H NMR, 13C NMR and mass studies. • Compounds (1–7) were tested against the glutathione S-transferase (GST), acetylcholinesterase (AChE), and Butyrylcholinesterase (BChE). • Remarkable inhibitory effects were obtained against three tested metabolic enzymes. In this study, new 1,2,3-triazole derivatives containing chalcone core (1 – 7) were synthesized. Obtained compounds were characterized by IR, 1H NMR, 13C NMR, and mass studies. Characterized compounds (1–7) inhibitory effects were tested against the glutathione S-transferase (GST), acetylcholinesterase (AChE), and Butyrylcholinesterase (BChE). Their K i values were in the range of 5.88–11.13 µM on AChE, 5.08–15.12 µM on BChE, and 9.82–13.22 µM on GST. Remarkable inhibitory effects were obtained against three tested metabolic enzymes. Also, binding scores of the best-inhibitors against AChE, BChE, and GST enzymes were detected as −9.969 kcal/mol, −10.672 kcal/mol, and −8.832 kcal/mol, respectively. Isoindoline-1,3-dione and benzothiophene moieties played a critical role in the inhibition of AChE and BChE enzymes, respectively. Phenylene and triazole moieties had the most important interactions for inhibition of the GST enzyme. Therefore, in vivo and in silico results indicated that these compounds can be considered in drug design processes for the treatment of some diseases including Alzheimer's disease (AD), leukemia, and some type of cancer. [ABSTRACT FROM AUTHOR]

• Some Novel heterocyclic N -Mannich bases were synthesized by reacting 1,2,4-triazole derivatives, morpholine, and formaldehyde. • The synthesized compounds' structures were identified through analytical techniques, including 1H/13C-NMR, IR, and elemental analysis. • The newly synthesized compounds were screened for their in vitro and in silico glutathione s-transferase enzyme inhibitory activity. • The synthesized compounds' absorption distribution, metabolism, excretion properties (ADME), molecular properties, toxicity, and bioactivity scores were calculated. The reaction of variously substituted 1,2,4-triazole derivatives with morpholine and formaldehyde represents an efficient and easy-to-set synthetic entry toward heterocyclic N -Mannich bases. For this purpose, the synthesized Schiff Bases (3a-g) were reacted with formaldehyde and morpholine, a secondary amine, to yield novel N -Mannich bases (6a-g). The structures of the compounds (6a-g) were determined structurally by employing 1H/13C-NMR, IR, and elemental analysis. The synthesized compounds were screened for in vitro biological activity, and the bioanalysis results showed that the newly synthesized compounds had different in vitro enzyme inhibition activities against Glutathione S-transferase (GST). Their K i values were calculated in the 2.69 ± 0.421–21.58±6.809 µM range. Besides, their IC 50 values were calculated in the 1.975–2.753 µM range. Also, the potential inhibitory effects of the synthesized compounds on glutathione S-transferase enzyme were evaluated by in silico method. The highest affinity values for inhibition of glutathione S-transferase enzyme were observed as 6c (−7.7 kcal/mol), 6 g (−7.4 kcal/mol), and 6b (−6.8 kcal/mol), respectively, and they gave better affinity values than standard Ethacrynic acid. Furthermore, the absorption distribution, metabolism, and excretion properties (ADME), molecular properties, toxicity estimation, and compounds' bioactivity scores were evaluated. [ABSTRACT FROM AUTHOR]