Effect of fentanyl and remifentanil on neuron damage and oxidative stress during induction neurotoxicity.

Opioids can be used for medical and non-medical purposes. Chronic pain such as cancer, as well as the frequent use of such drugs in places such as operating rooms and intensive care units, and in non-medical areas like drug abuse the effects and side effects of these drugs need to be examined in more detail. For this purpose, the effects of fentanyl and remifentanil drugs on neuroinflammation, oxidative stress and cholinesterase metabolism were investigated. Neuron cells (CRL-10742) were used for the evaluation of the toxicity of fentanyl and remifentanil. MTT, PON1 activity and total thiol levels for its effect on oxidative stress, AChE and BChE activities for its effect on the cholinergic system, and TNF, IL-8 and IL-10 gene levels for its neuroinflammation effect were determined. The highest neurotoxic dose of fentanyl and remifentanil was determined as 10 µg/mL. It was observed that the rate of neuron cells in this dose has decreased by up to 61.80% and 56.89%, respectively. The IL-8 gene expression level in both opioids was down-regulated while IL 10 gene level was up-regulated in a dose-dependent manner compared to the control. In our results, the TNF gene expression level differs between the two opioids. In the fentanyl group, it was seen to be up-regulated in a dose-dependent manner compared to the control. Fentanyl and remifentanil showed an inhibitory effect against PON1, while remifentanil showed an increase in total thiol levels. PON1, BChE and total thiol activities showed similarity with MTT.

Explainable artificial intelligence in the design of selective carbonic anhydrase I-II inhibitors via molecular fingerprinting.

Inhibiting the enzymes carbonic anhydrase I (CA I) and carbonic anhydrase II (CA II) presents a potential avenue for addressing nervous system ailments such as glaucoma and Alzheimer's disease. Our study explored harnessing explainable artificial intelligence (XAI) to unveil the molecular traits inherent in CA I and CA II inhibitors. The PubChem molecular fingerprints of these inhibitors, sourced from the ChEMBL database, were subjected to detailed XAI analysis. The study encompassed training 10 regression models using IC50 values, and their efficacy was gauged using metrics including R2, RMSE, and time taken. The Decision Tree Regressor algorithm emerged as the optimal performer (R2: 0.93, RMSE: 0.43, time-taken: 0.07). Furthermore, the PFI method unveiled key molecular features for CA I inhibitors, notably PubChemFP432 (C(O)N) and PubChemFP6978 (C(O)O). The SHAP analysis highlighted the significance of attributes like PubChemFP539 (C(O)NCC), PubChemFP601 (C(O)OCC), and PubChemFP432 (C(O)N) in CA I inhibitiotable n. Likewise, features for CA II inhibitors encompassed PubChemFP528(C(O)OCCN), PubChemFP791 (C(O)OCCC), PubChemFP696 (C(O)OCCCC), PubChemFP335 (C(O)NCCN), PubChemFP580 (C(O)NCCCN), and PubChemFP180 (C(O)NCCC), identified through SHAP analysis. The sulfonamide group (S), aromatic ring (A), and hydrogen bonding group (H) exert a substantial impact on CA I and CA II enzyme activities and IC50 values through the XAI approach. These insights into the CA I and CA II inhibitors are poised to guide future drug discovery efforts, serving as a beacon for innovative therapeutic interventions.

Dynamics of small molecule-enzyme interactions: Novel benzenesulfonamides as multi-target agents endowed with inhibitory effects against some metabolic enzymes.

In contemporary medicinal chemistry, employing a singular small molecule to concurrently multi-target disparate molecular entities is emerging as a potent strategy in the ongoing battle against metabolic disease. In this study, we present the meticulous design, synthesis, and comprehensive biological evaluation of a novel series of 1,2,3-triazolylmethylthio-1,3,4-oxadiazolylbenzenesulfonamide derivatives (8a-m) as potential multi-target inhibitors against human carbonic anhydrase (EC.4.2.1.1, hCA I/II), α-glycosidase (EC.3.2.1.20, α-GLY), and α-amylase (EC.3.2.1.1, α-AMY). Each synthesized sulfonamide underwent rigorous assessment for inhibitory effects against four distinct enzymes, revealing varying degrees of hCA I/II, a-GLY, and a-AMY inhibition across the tested compounds. hCA I was notably susceptible to inhibition by all compounds, demonstrating remarkably low inhibition constants (KI) ranging from 42.20 ± 3.90 nM to 217.90 ± 11.81 nM compared to the reference standard AAZ (KI of 439.17 ± 9.30 nM). The evaluation against hCA II showed that most of the synthesized compounds exhibited potent inhibition effects with KI values spanning the nanomolar range 16.44 ± 1.53-70.82 ± 4.51 nM, while three specific compounds, namely 8a-b and 8d, showcased lower inhibitory potency than other derivatives that did not exceed that of the reference drug AAZ (with a KI of 98.28 ± 1.69 nM). Moreover, across the spectrum of synthesized compounds, potent inhibition profiles were observed against diabetes mellitus-associated α-GLY (KI values spanning from 0.54 ± 0.06 µM to 5.48 ± 0.50 µM), while significant inhibition effects were noted against α-AMY, with IC50 values ranging between 0.16 ± 0.04 µM and 7.81 ± 0.51 µM) compared to reference standard ACR (KI of 23.53 ± 2.72 µM and IC50 of 48.17 ± 2.34 µM, respectively). Subsequently, these inhibitors were evaluated for their DPPH· and ABTS+· radical scavenging activity. Moreover, molecular docking investigations were meticulously conducted within the active sites of hCA I/II, α-GLY, and α-AMY to provide comprehensive elucidation and rationale for the observed inhibitory outcomes.

Design and Synthesis of Pyrazole Carboxamide Derivatives as Selective Cholinesterase and Carbonic Anhydrase Inhibitors: Molecular Docking and Biological Evaluation.

The present study focused on the synthesis and characterization of novel pyrazole carboxamide derivatives (SA1-12). The inhibitory effect of the compounds on cholinesterases (ChEs; AChE and BChE) and carbonic anhydrases (hCAs; hCA I and hCA II) isoenzymes were screened as in vitro. These series compounds have been identified as potential inhibitors with a KI values in the range of 10.69±1.27-70.87±8.11 nM for hCA I, 20.01±3.48-56.63±6.41 nM for hCA II, 6.60±0.62-14.15±1.09 nM for acetylcholinesterase (AChE) and 54.87±7.76-137.20 ±9.61 nM for butyrylcholinesterase (BChE). These compounds have a more effective inhibition effect when compared to the reference compounds. In addition, the potential binding positions of the compounds with high affinity for ChE and hCAs were demonstrated by in silico methods. The results of in silico and in vitro studies support each other. As a result of the present study, the compounds with high inhibitory activity for metabolic enzymes, such as ChE and hCA were designed. The compounds may be potential alternative agents used as selective ChE and hCA inhibitors in the treatment of Alzheimer's disease and glaucoma.

Phenolic Content Analysis of Two Species Belonging to the Lamiaceae Family: Antioxidant, Anticholinergic, and Antibacterial Activities.

The Lamiaceae family are utilized as ornamental, medicinal, and food supplements throughout the world. The current study focuses on a comparative analysis of the phenolic compositions and bioactivities (including antioxidant, anticholinergic, and antibacterial activities) of ethanolic extracts derived from the aerial parts of the two species (Lavandula stoechas L. and Thymus sipyleus Boiss). The presence of phenolic compounds and phytochemicals in the plant extracts was identified using the LC-MS/MS technique. The LC-MS/MS analysis revealed that vanillic acid (125,596.66 µg/L) was the most abundant phytochemical in L. stoechas. Kaempferol (8550.52 µg/L) was the most abundant substance in Thymus sipyleus. The assessment of the antioxidant efficacy of the species extracts was conducted using the DPPH (2.2-diphenyl-1-picryl-hydrazyl-hydrate), ABTS (2.2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)), Fe3+-Fe2+ reducing, and CUPRAC (Cu2+-Cu+ reducing) assays. The anticholinergic activity of the samples was determined using the acetylcholinesterase (AChE) inhibition assay. The results of antioxidant activity were higher in the T. sipyleus than in the L. stoechas ethanol extracts. The extracts of L. stoechas exhibited radical scavenging activity ranging from 15 to 18%, while T. sipyleus had activity effects ranging from 34% to 38%. The AChE inhibition potential for L. stoechas and T. sipyleus extracts as IC50 values were 0.221 ± 0.01 mg/mL and 0.067 ± 0.02 mg/mL, respectively. The antibacterial effects of the ethanolic extracts of these species against pathogenic bacteria isolates were determined using the MIC (minimal inhibitory concentration) method. These findings indicated that the extracts from L. stoechas and T. sipyleus possess the potential to be natural antioxidants in the realm of food preservation. Additionally, their antioxidant, anticholinergic, and antimicrobial properties suggest potential therapeutic utility in the management of certain diseases.

Evaluation of the relationship among gene expressions and enzyme activities with antioxidant role and presenilin 1 expression in Alzheimer's disease.

It is known that oxidative stress originating from reactive oxygen species plays a role in the pathogenesis of Alzheimer's disease. In this study, the role of antioxidant status associated with oxidative stress in Alzheimer's disease was investigated. Peripheral blood samples were obtained from 28 healthy individuals (as control) and 28 Alzheimer's patients who met the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria. Catalase, glutathione S-transferase and paraoxonase 1 enzyme activities in blood plasma and glutathione S-transferase enzyme activities in erythrocytes were determined by spectrophotometer. Catalase, glutathione S-transferase and presenilin 1 gene expressions in leukocytes were determined using qRT-PCR. Data were analysed with SPSS one-way anova, a LSD post hoc test at p < 0.05. The activity of each enzyme was significantly reduced in Alzheimer's patients compared to control. The catalase gene expression level did not change compared to the control. Glutathione S-transferase and presenilin 1 gene expression levels were increased compared to the control.

Novel bis-ureido-substituted sulfaguanidines and sulfisoxazoles as carbonic anhydrase and acetylcholinesterase inhibitors.

To discover alternative substances to compounds used to treat many diseases, especially treating Alzheimer's disease (AD) and Parkinson's disease targeting carbonic anhydrase (hCA) and acetylcholinesterase (AChE) enzymes, is important. For this purpose, a series of novel bis-ureido-substituted sulfaguanidine (SG1-4) and sulfisoxazole (SO1-4) derivatives were synthesized, and their inhibitory capacities were screened against hCA isoenzymes (hCA I and II) and AChE. Possible binding mechanisms of inhibitors to the active site were elucidated by in silico studies, and the results were supported by in vitro results. Moreover, the percent radical scavenging capacities of the derivatives were also evaluated. The derivatives (SG1-4 and SO1-4) were more effective against hCAs compared to standard drug acetazolamide (KI values of 98.28-439.17 nM for hCA I and II, respectively) and exhibited the highest inhibition with the KIs in the ranges of 2.54 ± 0.50-41.02 ± 7.52 nM for hCA I, 11.20 ± 2.97-67.14 ± 13.58 nM for hCA II, and 257.60 ± 27.84-442.60 ± 52.13 nM for AChE. Also, compounds SG1 and SO1 also showed ABTS radical scavenging activity at the rate of 70% and 78%, respectively. These results will contribute to the literature for the rational design and synthesis of new potent and selective inhibitors targeting hCAs and AChE with multifunctional effects such as radical scavenging as well as inhibition. This study focused on the synthesis and inhibitory effects of bis-ureido-substituted sulfaguanidine (SG1-4) and sulfisoxazole (SO1-4) derivatives against human hCA I and II isoforms and AChE. In order to test synthesized derivatives' free radical scavenging potentials were the DPPH and ABTS assays. In silico studies elucidated possible binding mechanisms of inhibitors to the active site.

Synthesis and Characterization of Novel 1,3-Diaryltriazene-Substituted Sulfaguanidine Derivatives as Selective Carbonic Anhydrase Inhibitors: Biological Evaluation, in Silico ADME/T and Molecular Docking Study.

Sulfonamide compounds known as human carbonic anhydrase (hCA) inhibitors are used in the treatment of many diseases such as epilepsy, antibacterial, glaucoma, various diseases. 1,3-diaryl-substituted triazenes and sulfaguanidine are used for therapeutic purposes in many drug structures. Based on these two groups, the synthesis of new compounds is important. In the present study, the novel 1,3-diaryltriazene-substituted sulfaguanidine derivatives (SG1-13) were synthesized and fully characterized by spectroscopic and analytic methods. Inhibitory effect of these compounds on the hCA I and hCA II was screened as in vitro. All the series of synthesized compounds have been identified as potential hCA isoenzymes inhibitory with KI values in the range of 6.44±0.74-86.85±7.01 nM for hCA I and with KI values in the range of 8.16±0.40-77.29±9.56 nM for hCA II. Moreover, the new series of compounds showed a more effective inhibition effect than the acetazolamide used as a reference. The possible binding positions of the compounds with a binding affinity to the hCA I and hCA II was demonstrated by in silico studies. In conclusion, compounds with varying degrees of affinity for hCA isoenzymes have been designed and as selective hCA inhibitors. These compounds may be potential alternative agents that can be used to treat or prevent diseases associated with glaucoma and hCA inhibition.

Anticholinergic, Antioxidant, and Antibacterial Properties of Vitex Agnus-Castus L. Seed Extract: Assessment of Its Phenolic Content by LC/MS/MS.

In this current study, Vitex agnus-castus seed ethanol extracts were analyzed for their phytochemical component content, anticholinergic and antioxidant activities, and antibacterial properties. The phenolic compound composition of these seeds was determined by using LC/MS/MS. Antioxidant activity of the seeds was examined by the DPPH, ABTS, Fe3+ -Fe2+ reducing, and CUPRAC. Also, the anticholinergic activity was measured by the inhibition of acetylcholinesterase (AChE). The antibacterial activity was performed by disc diffusion and minimum inhibitory concentration methods. The main phenolic compound was vanillic acid (22812.05 µg/L) and followed by luteolin, fumaric acid, quercetin, caffeic acid, 4-hydroxybenzoic acid, salicylic acid, kaempferol, butein, ellagic acid, resveratrol, catechin hydrate, phloridzin dehydrate, naringenin, respectively. The DPPH free radical scavenging value of ethanol extract of plant seeds was 9.41 %, while the ABTS radical scavenging activity was determined as 12.66 %. The ethanol extract of the seeds exhibited antibacterial activity on Escherichia coli, Staphylococcus aureus, and Salmonella Typhimurium, differently. S. aureus was found to be more susceptible to the extract than other bacteria. Also, the inhibition effect of seed ethanolic extract on the AChE with IC50 values were 36.34±5.6 µg/mL. From the results, V. agnus-castus seed can be suggested as a promising natural antioxidant and antibacterial candidate for the preservation of foods.

The relationship between overactive bladder and attachment: A preliminary study.

AIM: There are strong relationships between overactive bladder (OAB) and psychological factors. The aim of this study was to examine the relationship between OAB and attachment. METHODS: Patients who presented with OAB symptoms and were first diagnosed with OAB were included in the study. Patient and control groups were matched in terms of age and gender. A urological and psychiatric examination was performed on each participant. The severity of patients' OAB symptoms was assessed using the Overactive Bladder-V8 Questionnaire (OAB-v8). The characteristics of attachment patterns were evaluated using The Close Relationships Scale Revised. RESULTS: The OAB and control groups included 41 and 43 participants, respectively. No significant difference was found between the two groups with regard to alcohol abuse, daily cigarette consumption, marital status, and gender. The prevalence of anxious attachment was significantly higher in the OAB group than in the control group (p < 0.001), whereas no significant difference was found with regard to avoidant attachment (p = 0.18). A significant relationship was found between the OAB-v8 score and anxious attachment in OAB patients (r = 0.50; p < 0.001). CONCLUSIONS: Our findings suggest that insecure attachment, especially anxious attachment is associated with OAB and the severity of OAB symptoms. More extensive and longitudinal studies can better show the relationship between attachment and OAB. Future research may focus on the possibility of causality between attachment and OAB.

Biological effects of bis-hydrazone compounds bearing isovanillin moiety on the aldose reductase.

Aldose reductase (ALR2), one of the metabolically important enzymes, catalyzes the formation of sorbitol from glucose in the polyol pathway. ALR2 inhibition is required to prevent diabetic complications. In the present study, the novel bis-hydrazone compounds bearing isovanillin moiety (GY1-12) were synthesized, and various chromatographic methods were applied to purify the ALR2 enzyme. Afterward, the inhibitory effect of the synthesized compounds on the ALR2 was screened in vitro. All the novel bis-hydrazones demonstrated activity in nanomolar levels as AR inhibitors with IC50 and KI values in the range of 12.55-35.04 nM, and 13.38-88.21 nM, respectively. Compounds GY-11, GY-7, and GY-5 against ALR2 were identified as the highly potent inhibitors, respectively, and were superior to the standard drug, epalrestat. Moreover, a comprehensive ligand-receptor interactions prediction was performed using ADME-Tox, Glide XP, and MM-GBSA modules of Schrödinger Small-Molecule Drug Discovery Suite to elucidate the novel bis-hydrazone derivatives, potential binding modes versus the ALR2. As a result, these compounds with ALR2 inhibitory effects may be potential alternative agents that can be used to treat or prevent diabetic complications.

Conducting polymer-based electrochemical biosensor for the detection of acetylthiocholine and pesticide via acetylcholinesterase.

A voltammetric biosensor for acetylthiocholine (ATCh) and paraoxon detection was successfully developed. To achieve this goal, polypyrrole (PPy) was synthesized onto the platinum (Pt) electrode surface in 0.30 M oxalic acid solution containing 25 mM pyrrole. PPy-coated Pt (Pt/PPy) electrode surface was covered with chitosan (Chi) (Pt/PPy/Chi). The acetylcholinesterase (AChE) enzyme was immobilized on the Pt/PPy/Chi electrode surface to build a voltammetric biosensor (Pt/PPy/Chi/AChE). The storage stability of the biosensor was determined to be 72% even after 60 days. The operational stability was determined to be 94% after 20 consecutive measurements. For the biosensor, the linear range was determined to be 30-50 µM for ATCh and 0.46-1.84 nM for paraoxon. The limit of detection (LOD) was determined to be 0.45 µM for ATCh and 0.17 nM for paraoxon.

Synthesis, Characterization, and Inhibition Study of Novel Substituted Phenylureido Sulfaguanidine Derivatives as α-Glycosidase and Cholinesterase Inhibitors.

A series of six N-carbamimidoyl-4-(3-substituted phenylureido)benzenesulfonamide derivatives were synthesized by reaction of sulfaguanidine with aromatic isocyanates. In vitro and in silico inhibitory effects of the novel ureido-substituted sulfaguanidine derivatives were investigated by spectrophotometric methods for α-glycosidase (α-GLY), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes associated with diabetes mellitus (DM) and Alzheimer's disease (AD). N-Carbamimidoyl-4-{[(3,4-dichlorophenyl)carbamoyl]amino}benzene-1-sulfonamide (2f) showed AChE and BChE inhibitory effects, with KI values of 515.98±45.03 nM and 598.47±59.18 nM, respectively, while N-carbamimidoyl-4-{[(3-chlorophenyl)carbamoyl]amino}benzene-1-sulfonamide (2e) showed strong α-GLY inhibitory effect, with KI values of 103.94±13.06 nM. The antidiabetic effects of the novel synthesized compounds are higher than their anti-Alzheimer's effects, because the inhibition effect of the compounds on the α-GLY with diabetic enzyme is greater than the effect on esterase enzymes. Indeed, inhibition of the metabolic enzymes is important for the treatment of DM and AD.

Synthesis, characterization, inhibition effects, and molecular docking studies as acetylcholinesterase, α-glycosidase, and carbonic anhydrase inhibitors of novel benzenesulfonamides incorporating 1,3,5-triazine structural motifs.

Some metabolic enzyme inhibitors can be used in the treatment of many diseases. Therefore, synthesis and determination of alternative inhibitors are essential. In this study, the inhibition effect of newly synthesized compounds on carbonic anhydrase (cytosolic isoforms, hCA I and hCA II), α-glycosidase (α-GLY), and acetylcholinesterase (AChE) were investigated. The possible binding mechanism of the compounds with a high inhibitory effect on the active site of the enzyme was demonstrated by molecular docking method. We investigated the inhibition effects of novel synthesized compounds (MZ1-MZ11) on metabolic enzymes such as α-GLY, AChE, and hCA I and II. The compound MZ6 for AChE, MZ8 for CA I and CA II and MZ7 for α-GLY showed a very active inhibition profile (KIs 51.67 ± 4.76 for hCA I, 40.35 ± 5.74 nM for hCA II, 41.74 ± 8.08 nM for α-GLY and 335.76 ± 46.91 nM for AChE). The novel synthesized compounds (MZ1-MZ11) have a higher enzyme (α-GLY, AChE, hCA I, and II) inhibitory potential than ACR, TAC, and AZA, respectively. The compounds may have the potential to be used as alternative medicines after further research in the treatment of many diseases such as diabetes, Alzheimer's disease, heart failure, ulcer, and epilepsy.

Synthesis, characterisation, biological evaluation and in silico studies of sulphonamide Schiff bases.

Sulphonamides are biologically important compounds with low toxicity, many bioactivities and cost-effectiveness. Eight sulphonamide derivatives were synthesised and characterised by FT-IR, 13C NMR, 1H NMR, LC-MS and elemental analysis. Their inhibitory effect on AChE, and carbonic anhydrase I and II enzyme activities was investigated. Their antioxidant activity was determined using different bioanalytical assays such as radical scavenging tests with ABTS•+, and DPPH•+ as well as metal-reducing abilities with CUPRAC, and FRAP assays. All compounds showed satisfactory enzyme inhibitory potency in nanomolar concentrations against AChE and CA isoforms with KI values ranging from 10.14 ± 0.03 to 100.58 ± 1.90 nM. Amine group containing derivatives showed high metal reduction activity and about 70% ABTS radical scavenging activity. Due to their antioxidant activity and AChE inhibition, these novel compounds may be considered as leads for investigations in neurodegenerative diseases.

Synthesis, characterization, biological evaluation, and in silico studies of novel 1,3-diaryltriazene-substituted sulfathiazole derivatives.

In the present study, a series of eleven novel 1,3-diaryltriazene-substituted sulfathiazole moieties (ST1-11) was synthesized by the reaction of diazonium salt of sulfathiazole with substituted aromatic amines and their chemical structures were characterized by Fourier transform infrared, 1 H-NMR (nuclear magnetic resonance), 13 C-NMR, and high-resolution mass spectroscopy methods. These synthesized novel derivatives were found to be effective inhibitor molecules for α-glycosidase (α-GLY), human carbonic anhydrase (hCA), and acetylcholinesterase (AChE), with KI values in the range of 426.84 ± 58.42-708.61 ± 122.67 nM for α-GLY, 450.37 ± 50.35-1,094.34 ± 111.37 nM for hCA I, 504.37 ± 57.22-1,205.36 ± 195.47 nM for hCA II, and 68.28 ± 10.26-193.74 ± 19.75 nM for AChE. Among the synthesized novel compounds, several lead compounds were investigated against the tested metabolic enzymes. More specifically, ST11 (4-[3-(perfluorophenyl)triaz-1-en-1-yl]-N-(thiazol-2-yl)benzenesulfonamide) showed a highly efficient inhibition profile against hCA I, hCA II, and AChE, with KI values of 450.37 ± 50.35, 504.37 ± 57.22, and 68.28 ± 10.26 nM, respectively. Due to its significant biological inhibitory potency, this derivative may be considered as an interesting lead compound against these enzymes.

Vitamin B12, folate levels and somatoform dissociation in conversion disorder.

OBJECTIVE: To evaluate the association of folate and vitamin B12 levels in patients with conversion disorder, and to illuminate the aetiology of conversion disorder by examining depression and somatoform dissociation. METHODS: The case-control study was conducted from March 2014 to May 2015 at the Medical Centre of Yuzuncu Yil University, Van, Turkey, and comprised patients diagnosed with conversion disorder and healthy controls. Blood samples were taken from both groups for vitamin B12 and folate levels. Data was collected using the Beck Depression Inventory and Somatoform Dissociation Scale. Data was analysed using SPSS 18. RESULTS: Of the 100 subjects, 55(55%) were cases with a mean age of 27.05±9.04 years and 45(45%) were controls with a mean age of 26.56± 5.96 years. The mean level of B12 was 283.93±122.96 in cases and 324.62±128.82 in controls (p=0.05). The mean level of folic acid was 5.47±1.84 in cases and 6.07±2.26 in controls (p>0.05). CONCLUSIONS: Physicians need to be vigilant about vitamin B12 levels in patients with conversion symptoms.

The Binding Mechanisms and Inhibitory Effect of Intravenous Anesthetics on AChE In Vitro and In Vivo: Kinetic Analysis and Molecular Docking.

Inhibitors of acetylcholinesterase (AChE), which have an important role in the prevention of excessive AChE activity and ß-amyloid (Aß) formation are widely used in the symptomatic treatment of Alzheimer's disease (AD). The inhibitory effect of anesthetic agents on AChE was determined by several approaches, including binding mechanisms, molecular docking and kinetic analysis. Inhibitory effect of intravenous anesthetics on AChE as in vitro and in vivo have been discovered. The midazolam, propofol and thiopental have shown competitive inhibition type (midazolam > propofol > thiopental) and Ki values were found to be 3.96.0 ± 0.1, 5.75 ± 0.12 and 29.65 ± 2.04 µM, respectively. The thiopental and midazolam showed inhibition effect on AChE in vitro, whereas they showed activation effect in vivo when they are combined together. The order of binding of the drugs to the active site of the 4M0E receptor was found to be midazolam > propofol > thiopental. This study on anesthetic agents that are now widely used in surgical applications, have provided a molecular basis for investigating the drug-enzyme interactions mechanism. In addition, the study is important in understanding the molecular mechanism of inhibitors that are effective in the treatment of AD.

Phenolic compounds inhibit the aldose reductase enzyme from the sheep kidney.

Aldose reductase (AR) is the key enzyme for the polyol pathway and responsible for sorbitol accumulation during the hyperglycemia. The present article focuses on the role of phenol, pyrogallol, hydroquinone, resorcinol, catechol, and phloroglucinol in in vitro inhibition of AR. For this purpose, AR was purified from the sheep kidney with 5.33 EU mg-1 specific activity and 0.64% yield using several chromatographic methods. Various concentrations of the compounds were tested on in vitro AR activity. IC50 values were found for phenol, pyrogallol, hydroquinone, resorcinol, catechol, and phloroglucinol as 6.5, 1.13, 5.45, 2.21, 1.8, and 2.09 mM, respectively, and their Ki constant was calculated as 3.45 ± 0.92, 0.96 ± 0.28, 3.07 ± 0.46, 1.59 ± 0.43, 2.5 ± 0.35, and 2.54 ± 0.45 mM, respectively. Pyrogallol showed better inhibitory effect compared to the other compounds. The inhibition mechanisms of all compounds were noncompetitive. In the presents study, in vitro AR inhibition was examined by the phenolic compounds.

Isolation of phenolic compounds from eco-friendly white bee propolis: Antioxidant, wound-healing, and anti-Alzheimer effects.

This study presents the first findings regarding extraction, isolation, enzyme inhibition, and antioxidant activity. The oral mucosal wound-healing process was investigated using propolis water extract (PWE) incubation with gingival fibroblast cells and concluded that propolis was effective on the oral mucosal wound-healing pattern compared to untreated controls. Additionally, phenolic compounds (fraxetin, apigenin, galangin, pinobanksin, chrysin, etc.) were isolated from propolis, and their chemical structures were elucidated using comprehensive spectroscopic methods. The antioxidant and anti-Alzheimer potential activities of PWE and some isolated compounds were screened and revealing their inhibitory effects on acetylcholinesterase (AChE) with IC50 values ranging from 0.45 ± 0.01 to 1.15 ± 0.03 mM, as well as remarkable free-radical scavenging and metal reduction capacities. The results suggest that these compounds and PWE can be used as therapeutic agents due to their antioxidant properties and inhibitory potential on AChE. It can also be used for therapeutic purposes since its wound-healing effect is promising.