BChE Enzymes Research Articles

Diversely functionalized benzopyran scaffolds as potential lead candidates for treating Alzheimer's disease and diabetes

The current study deals with the preparation of polyfunctional benzopyran derivatives 1–25, synthesized by the condensation of 2,4-dihydroxy benzophenone, substituted aldehydes, and malononitrile. These compounds were evaluated for their inhibitory potential against AChE, BChE, α-amylase, and α-glucosidase enzymes, as well as for DPPH radical scavenging activity. Among 25 compounds, 1, 4–6, 14, 15, and 25 showed excellent inhibition against AChE (IC50 = 5.30 - 37.14 µM) and BChE (IC50 = 8.20 - 43.13 µM), compared to standard donepezil (IC50 = 40.05 for AChE; 45.00 µM for BChE), respectively. Moreover, compounds 2, 3, 11, and 12 inhibited α-amylase (IC50 = 1.88 - 11.42 µM) and α-glucosidase (IC50 = 2.54 - 8.36 µM) with greater potency than the standard acarbose (IC50 = 14.65 µM). Kinetic studies of the active compounds were also carried out to find the mode of inhibition. Furthermore, molecular docking was performed to determine the ligands' interaction with the enzyme's active site. In addition, compounds 9, 19, and 21 exhibited significant DPPH radical scavenging activity (SC50 = 44.88 - 64.61 µM) compared to BHT (SC50 = 66.34 µM). Thus, this study suggests that the reported compounds hold the potential to be further advanced as lead anti-Alzheimer and anti-diabetic agents.

In vitro antioxidant and in silico enzyme inhibition studies of Carissa carandas Linn.: potential ingredient for nutraceutical development

ABSTRACT Carissa carandas L. is a wild food plant, however, is cultivated for its fruits to be utilized to make pickles, jams, and other similar products. Fruit of this plant has been intensively investigated for its bioactive potential; however, a scanty study is reported on the leaf, which is usually wasted. In the present study, ethanolic extract of the leaf of C. carandas was analyzed for its total bioactive contents and found rich in phenolics and flavonoids (26.67 ± 0.33 mg GAE/g extract and 18.42 ± 0.05 mg RE/g extract, respectively). These findings were substantiated due to UHPLCMS/MS analysis, which disclosed the presence of about 110 secondary metabolites, mostly lignans, flavonoids, and terpenoids. In DPPH and ABTS free radical inhibition assays, the extract showed inhibitory values as 47.51 ± 0.09 and 93.09 ± 2.8 mg TE/g extract, respectively. Its further antioxidant potential was observed in CUPRAC and FRAP assays, wherein the metal reducing power was recorded as 102.05 ± 1.03 and 67.24 ± 0.9 mg TE/g extract, respectively, while in phosphomolybdenum and metal chelating assays, the extract also disclosed potential activity (0.92 ± 0.02 mmol TE/g extract and 21.42 ± 0.34 mg EDTAE/g extract). The extract was also significantly active against tyrosinase (45.69 ± 0.7 mg KAE/g extract) and showed mild activities against AChE (3.61 ± 0.16 mg GALAE/g extract), BChE (1.43 ± 0.2 mg GALAE/g extract), α-amylase (0.46 ± 0.01 mmol ACAE/g extract) and α-glucosidase (1.05 ± 0.02 mmol ACAE/g extract). In computational studies, binding affinities for AChE and BChE enzymes were from −4.21 to −12.70 and −7.58 to −12.53 kcal/mol, respectively, confirming the results of the invitro tests and ADME studies. The current finding suggested that C. carandas may be considered as a source for several nutraceutical formulations.

Cousinia birandiana (Asteraceae): phytochemical composition, antioxidant and enzyme inhibition capacity

Cousinia birandiana is one of the widely spread species of the Asteraceae family. In this study, the total phenolic and flavonoid contents, the inhibitory effect on α-amylase, α-glucosidase, acetylcholinesterase and butyrylcholinesterase enzymes, the antioxidant capacity (by DPPH, ABTS, FRAP, CUPRAC tests) and the phytochemical content (by LC-HRMS) of the ethanol extract and fractions were studied. As a result, it was shown that ethanol extract has better enzyme inhibitory effects on α-amylase, AChE and BChE enzymes with 300.000, 380.605 and 133.567 µg/mL IC50 values. Besides that, the highest phenolic and flavonoid content was found in the ethyl acetate fraction (735.986 mgGAE/gextract and 952.317 mgCA/gextract, respectively). It is observed that the same fraction has better antioxidant activity in DPPH (IC50 =112.701 mg/mL), ABTS (9.494 µM Trolox/gextract) and CUPRAC (1120.454 mgGAE/gextract) tests and the n-hexane fraction has a higher FRAP (1351.199 mmol Fe2+/gextract) antioxidant effect. According to the phytochemical analyses quinic acid, chlorogenic acid and isoquercitrin were found as major compounds in the ethanol extract and fractions. In addition, the same assays were carried out with these major substances. So, this plant can be viewed as a promising bio-resource for pharmaceuticals and biomedical products.

Revisiting capsaicin and nonivamide: Their analogs exert strong inhibitory activity against cholinesterases

The scientific community has long been interested in capsaicin, and the extensive hunt for AChE and BChE enzyme inhibitors is still ongoing. In this investigation analogs of capsaicin, such as the pharmaceutical nonivamide, which is preferred in clinical settings for the topical treatment of pain, were explored in the search for appropriate inhibitors. Thus, to test their inhibitory effect on AChE and BChE, we synthesized a short series of derivatives derived from vanillylamide. Consequently, it was discovered that compounds 12, 34, and 35, which have Ki values in the sub-micromolar concentration range, are especially effective inhibitors. Compound 12 demonstrated dual mixed-type (competitive/uncompetitive) inhibitory activity for both enzymes; compound 34 showed selective mixed-type inhibitory activity for AChE, and compound 35 was found to have selective uncompetitive activity for AChE.

ESSENTIAL OIL CONTENTS AND BIOLOGICAL ACTIVITIES OF THYMUS CANOVIRIDIS JALAS AND THYMUS SIPYLEUS BOISS.

Objective: Members of the Lamiaceae family are considered to be major sources of bioactive therapeutic agents. Many of them are important medicinal and aromatic plants used in traditional and modern medicine and in the food, cosmetic and pharmaceutical industries. The aim of this study was to investigate in detail the biological activities and chemical composition of the essential oils of Thymus canoviridis Jalas and Thymus sipyleus Boiss. species belonging to the genus Thymus, one of the most important genera of the Lamiaceae family. Material and Method: The essential oil content of the species was determined by GC-MS. Antioxidant activities of the essential oils were determined using lipid peroxidation, DPPH free radical, ABTS cation radical and CUPRAC methods. In addition, cytotoxic activities against breast cancer (MCF-7) and colon cancer (HT-29) cell lines and anticholinesterase (against AChE and BChE enzymes), urease, tyrosinase, elastase, collagenase and angiotensin converting enzyme inhibition activities were determined. Result and Discussion: When the essential oil composition of T. sipyleus was analyzed, the major compounds were 1,8-cineole (eucalyptol) (18.16%), camphor (15.08%) and endo-borneol (11.63%), while T. canoviridis was found to be rich in carvacrol (72.88%). T. canoviridis showed high antioxidant activity in lipid peroxidation (IC50: 45.72±0.12 μg/ml), ABTS (IC50: 6.12±0.03 μg/ml) and CUPRAC (IC50: 5.31±0.01 μg/ml) methods. The selectivities of T. canoviridis and T. sipyleus species against MCF-7 cell line were 4.39 and 6.81, respectively. In the enzyme inhibition studies, both Thymus species showed moderate inhibition activity against BChE enzyme (Inhibition%: 57.88±1.14, 39.21±0.89, respectively). In addition, T. sipyleus showed moderate inhibition of elastase enzyme (Inhibition%: 25.33±0.79). When the results are evaluated in general, it can be said that T. canoviridis essential oil with its rich carvacrol content and high cytotoxic and antioxidant activity can be preferred as a safer and natural option instead of synthetic preservatives in food, pharmaceutical and cosmetic industries to extend shelf life and ensure food safety.

Comprehensive phytochemical analysis of Salvia hispanica L. callus extracts using LC-MS/MS.

In this research, the study utilized the root, leaf, and petiole parts of in vitro grown Salvia hispanica plants as explants. Following UV-C treatment applied to developing callus, methanol extracts were obtained and analyzed using liquid chromatography-mass spectrometry (LC/MS) to investigate their anticancer properties. First, the seeds of S. hispanica were soaked in commercial bleach for 6 min to ensure surface sterilization. The most effective antimicrobial activity on Gram-negative bacteria, with a zone diameter (11 ± 0.82 mm), was noticed in callus extracts obtained from the petiole explant in the second protocol against Klebsiella pneumoniae EMCS bacteria. Anticancer activities on SH-SY5Y human neuroblastoma cells were investigated by using 1000, 500, 250, 125, 62.5, 31.25, 15.62, and 78.12 μg/mL doses of the extracts, and the most effective cytotoxic activity was determined at the 1000 μg/mL dose of the extracts obtained from both protocols. The extracts were determined to inhibit hCAI, hCAII, AChE, and BChE enzymes. The content of 53 different phytochemical components of the extracts was analyzed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Rosmarinic acid, quinic acid, and caffeic acid were found in the highest concentration. The comprehensive LC-MS/MS analysis of S. hispanica extracts revealed a diverse array of phytochemical compounds, highlighting its potential for therapeutic applications.

Amelioration potential of synthetic oxime chemical cores against multiple sclerosis and Alzheimer's diseases: Evaluation in aspects of in silico and in vitro experiments

Alzheimer disease (AD) and multiple sclerosis (MS) are inflammatory neurological disorders. The main symptom of AD is dementia, and the main symptoms of MS are vertigo, sexual dysfunction, cognitive problems, and fatigue. Today, millions of people are affected by AD and MS, and the number is growing day by day. However, there are not any accurate remedies for both disorders. For this reason, discovering novel drug molecules against neurological disorders such as AD and MS is essential and precious. Oximes and benzofurans exhibit many pharmacological effects including anti-inflammatory and neurological activities. Thus, several novel compounds bearing oxime and benzofuran chemical cores were designed and synthesized, and their in vitro anticholinesterase activities were investigated in our previous study. A number of the synthesized molecules showed excellent anticholinesterase activity against both AChE and BChE enzymes. The mentioned study constituted a background for this study. In this study, we picked different chemical skeletons among all the synthesized molecules to conduct further in silico and in vitro experiments. In order to support our in vitro anticholinesterase findings, we also examined in silico anti-Alzheimer activity of the selected molecules. In addition, in silico and in vitro activities against MS disease of the synthesized molecules were investigated. Molecule 4 extraordinarily showed outstanding activity against AD disease both in silico and in vitro, as well as in silico activity against MS disease. This feature makes molecule 4 a possible drug lead molecule which is very limited in the market. On the other hand, molecule 1, a less substituted oxime skeleton, demonstrated the strongest in vitro activity against MS disease through in vitro anti-inflammatory effect. As an observation, molecule 4 was determined to be the most promising molecule to focus on in the further steps.

Phytochemical analysis of Robinia pseudoacacia flowers and leaf: quantitative analysis of natural compounds and molecular docking application

Phenolic compounds are widely found and well-known secondary metabolites in plants. Identification, and quantification of phenolic compounds, and determination of their biological activities reveal the unknown secrets of plants. Robinia pseudoacacia (RP) is known as the white-flowered false acacia and is distributed in Northern Anatolia in Turkey. Spectrophotometric and chromatographic techniques are used to identify the presence and amount of phenolics. In this study, RP flowers and leaves were extracted with methanol and analyzed by LC-MS/MS to determine their phytochemical content. Salicylic acid and syringic acid were found as major products in leaves and flowers. RP extracts have been reported to have antibacterial activity and BChE inhibitory properties. Therefore, the BChE and DD peptidase enzyme inhibitory properties of the main components salicylic acid and syringic acid were investigated by molecule docking (MolDock). According to MolDock results, syringic acid interacted with BChE and DD peptidase and was calculated as a MolDock score of -79.38, and -71.25, with binding energies -5.90, and -5.40 kcal/mol respectively. Salicylic acid interacted with BChE and DD peptidase and was calculated as a MolDock score of -63.54, and -66.18, with binding energies of -6.10, and -5.70 kcal/mol respectively. As a result, salicylic acid had higher binding energy in its interactions with BChE and DD peptidase enzymes. In theory, salicylic acid can be used as a good BChE and DD peptidase inhibitor.

Novel benzene sulfonamide-piperazine hybrid compounds: design, synthesis, antioxidant, enzyme inhibition activities and docking, ADME profiling studies.

Benzene sulfonamides are an important biological substituent for several activities. In this study, hybridization of benzene sulfonamide with piperazine derivatives were investigated for their antioxidant capacity and enzyme inhibitory potencies. Six molecules were synthesized and characterized. DPPH, ABTS, FRAP, CUPRAC, chelating and phosphomolybdemum assays were applied to evaluate antioxidant capacities. Results show that compounds have high antioxidant capacity and compound 4 has the best antioxidant activity among them. Compound 4 has higher antioxidant activity than references for FRAP (IC50: 0.08 mM), CUPRAC (IC50: 0.21 mM) and phosphomolybdenum (IC50: 0.22 mM) assays. Besides this, compound 4 has moderate DPPH and ABTS antioxidant capacity. Furthermore, enzyme inhibition activities of these molecules were investigated against AChE, BChE, tyrosinase, α-amylase and α-glucosidase enzymes. It was revealed that all compounds have good enzyme inhibitory potential except for α-amylase enzyme. The best inhibitory activities were observed for AChE with compound 5 the same value (IC50: 1.003 mM), for BChE with compounds 2 and 5 the same value (IC50: 1.008 mM), for tyrosinase compound 4 (IC50: 1.19 mM), and for α-glucosidase with compound 3 (IC50: 1.000 mM). Docking studies have been conducted with these molecules, and the results correlate well with the inhibitory assays.

Single-crystal X-ray structure, theoretical (Hirshfeld, electronic properties, NBO, NLO, RDG), and molecular docking studies of three phthalimidoethanesulfonamide derivatives

The three N-substituted-2-phtalimidoethanesulfonamide derivatives, 2-(1,3-dioxoisoindolin-2- yl)-N-(2-isopropylphenyl)ethane-1-sulfonamide (I), N-(2,6-dimethylphenyl)-2-(1,3-dioxoiso indolin-2-yl)ethane-1-sulfonamide (II) and 2-(2-(morpholinosulfonyl)ethyl) isoindoline-1,3‑dione (III), were analyzed using a combined approach including single-crystal X-ray diffraction (SC-XRD), theoretical calculations with Density Functional Theory (DFT), and molecular docking studies. Phthalimide and sulfonamide compounds have recently attracted attention for their inhibitory properties against AChE and BChE enzymes. In this study, molecular and crystal structures of compounds have been confirmed by the SC-XRD technique. Optimized molecular geometries and vibrational modes have been examined and compared to experimental results. Frontier molecular orbital (HOMO-LUMO) energies, molecular electrostatic potential (MEP), natural bond orbital (NBO) analysis, and non-linear optical (NLO) properties have been investigated by DFT/B3LYP/6–311G++(d,p) method. The reduced density gradient (RDG) analysis has been performed to analyze the non-covalent interactions. The Hirshfeld surfaces and 2D fingerprint analyses have been used to determine the intermolecular interactions of compounds. Moreover, in silico docking studies are performed to investigate the interactions between N-substituted-2-phtalimidoethane sulfonamide derivatives and AChE and BChE enzymes.

Bis‐Ureido‐Substituted Benzenesulfonamides: Evaluation of Their Antibacterial, Anticholinesterase, and Cytotoxicity Properties

AbstractIn this study, we present the re‐synthesis of a series of twelve bis‐ureido‐substituted benzenesulfonamides, focusing on their potential as antibacterial, anticholinesterase, and cytotoxic agents. First, the antibacterial assessment of these compounds indicated varying activity levels across different bacterial strains, with S. aureus displaying resistance to all compounds, while compounds 9 and 11 exhibited promise against E. faecalis with a MIC value of 31.25 μg/mL. Additionally, P. aeruginosa showed resistance to compounds containing 4‐aminobenzene sulfonamides, whereas derivatives such as (8–11) and compound 19 displayed notable activity against E. coli, comparable to Ampicillin. Second, their anticholinesterase activities were examined, with a focus on their potential role in addressing neurological disorders, particularly Alzheimer′s disease. The findings indicated that all synthesized compounds showed a significant inhibitory effect on both AChE and BChE enzymes. Compound 11 demonstrated the most effective inhibition on the AChE enzyme with an IC50 value of 0.2160±0.09 nM, while compound 18 exhibited the most potent inhibition on the BChE enzyme with an IC50 value of 0.2257±0.06 nM. Finally, cytotoxicity studies were conducted across various cell lines, including breast, lung, and prostate cancer cells and normal cells. The results revealed that compound 12 emerged as the most potent tested compound against breast cancer cells with no cytotoxic effect on CRL‐4010 normal breast epithelial cells. The research presented here not only highlights the multifaceted pharmacological potential of bis‐ureido‐substituted benzenesulfonamides, but also indicates their potential as versatile compounds for antibacterial, anticholinesterase, and cytotoxicity applications, opening up new avenues for drug discovery and development.

Chemical composition and biological activities of essential oils and extract of Eucalyptus citriodora Hook

In this study, the leaves of Eucalyptus citriodora Hook (Lemon-Scented Eucalyptus) were harvested and collected from Üzümlü neighborhood of Fethiye district of Muğla in 2021. Chemical content analysis of steam distillation and hydrodistillation of essential oils were determined by GC-MS, while phenolic content of methanol extract was determined by HPLC-DAD. Antioxidant activities of essential oils and methanol extracts were determined by DPPH radical removal, ABTS cation removal, β-carotene linoleic acid, and CUPRAC activity methods; Anticholinesterase activity against AChE and BChE enzymes was determined by Ellman method; and tyrosinase inhibition associated with melanin hyperpigmentation, α-amylase inhibition, and α-glucosidase inhibition activities associated with diabetes were determined as an in vitro. The bioactivities and chemical contents of E. citriodora species, a great value of, Türkiye, were determined, bringing new natural products to organic chemistry. As a result of the study, new bioactive extracts would be obtained and thus, they can effectively reveal the potential of new business opportunities. Since methanol extract is effective against incurable diseases such as Alzheimer's and diabetes, it will also be possible to develop therapeutics of such diseases by investigating the advanced chemistry and in vivo activities of the extracts with new projects.

In vitro and in silico based assessment of biological activity of endemic Allium species: LC-MS/MS analysis of onions

In this study, the beneficial biological activity of four Allium species was examined to determine the metabolite components, antioxidant, antimicrobial, antiproliferative, wound healing, and enzyme inhibitory activities. All in vitro tests were compared to their reference compounds. The quantitative phytochemical analysis was distinctively profiled fifteen metabolites. The extract of A. eldivanense exhibited promising inhibitory effect against AChE (IC50: 0.335 ± 0.04 mg mLˉˡ), BChE (IC50: 0.375 ± 0.04 mg mLˉˡ), α-glucosidase (IC50: 0.148 ± 0.01 mg mLˉˡ), and tyrosinase (IC50: 11.87 ± 1.07 μg mLˉˡ) enzymes. The extract from A. olympicum and A. ilgazense exhibited ABTS scavenging activity closer to that of BHT among four antioxidant assays. A. eldivanense showed antibacterial ability ranging from 4 to 8 mg mLˉˡ concentrations, and the extract is promising compared to ampicillin. A. peroninianum demonstrated the highest cytotoxic effect (IC50: 84.03 μg mLˉˡ) on cervical cancer cells, and all Allium extracts applied to the HeLa cell line significantly slowed down wound closure. The molecular implementation studies predicate the in vitro enzyme inhibitory findings, and the major compounds in the onion extract have the highest affinity for the targets. The findings suggested that Allium species have potential biological activities according to the comprehensive in vitro and in silico analysis.

The pharmacological properties of Gypsophila eriocalyx: The endemic medicinal plant of northern central Turkey

The aim of this study is to evaluate and compare the biological properties of different extracts (methanol, ethanol, and water) obtained from Gypsophila eriocalyx (G. eriocalyx), a medicinal plant traditionally used in Turkey. The components of different extracts were defined using the GC–MS method. The effects of G. eriocalyx extracts on cell proliferation, apoptosis, and cell cycle arrest in MDA-MB-231 breast cancer as well as in vitro antioxidant, enzyme inhibition, and antimicrobial activities were investigated. In accordance with the results obtained, although ethanol and methanol extracts of G. eriocalyx show higher antioxidant activity than G. eriocalyx water extract, enzyme inhibition activities of the extracts were not found to be significant compared to the reference drug. The methanol and ethanol extract of G. eriocalyx exhibited moderate antimicrobial activity against Staphylococcus aureus and methanol extract showed significant antimicrobial activity against Bacillus cereus. In addition, both extracts significantly inhibited cell viability in a dose-dependent manner in breast cancer cells. The cell growth inhibition by methanol and ethanol extracts induced S phase cell-cycle arrest and apoptosis in MDA-MB-231 cells. Lastly, in order to compare the activities of the chemicals found in Gypsophila eriocalyx plant extract, their activities against various proteins that are breast cancer protein (PDB ID:1A52 and 1JNX), antioxidant protein (PDB ID: 1HD2), AChE enzyme protein (PDB ID: 4M0E), BChE enzyme protein (PDB ID: 5NN0), and Escherichia coli protein (PDB ID: 4PRV)were compared. Then, ADME/T analysis calculations were made to examine the effects of molecules with high activity on human metabolism. Eventually, G. eriocalyx is thought to be a potent therapeutic herb that can be considered as an alternative and functional therapy for the management of diseases of a progressive nature related to oxidative damage such as infection, diabetes, cancer, and Alzheimer's disease.

Evaluation of antioxidant, antimicrobial, enzyme inhibition activity, and cell viability capacity of Hypericum heterophyllum vent., an endemic species in Turkey's Flora

The aim of this study was determined the antioxidant, antimicrobial, enzyme inhibition activity, and cell viability capacity of H. heterophyllum (endemic species in the Flora of Turkey) extracts. H. heterophyllum methanolic extract was used in this study. H. heterophyllum plants collected at the beginning of flowering and during full flowering. P content was determined with calorimetrically in spectrophotometer. K, CA, Mg, Fe, Mn, Zn and Cu was determined with Atomic Absorption and N concentration were determined according to the Kjeldahl distillation method. H. heterophyllum (endemic species in the Flora of Turkey) extract was evaluated for its antioxidant (DPPH, ABTS, total phenol and flavonoid content), antimicrobial (four bacteria (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus cereus) and two Candida species (Candida albicans and Candida tropicalis)), enzyme inhibition activity (ɑ-glucosidase, ɑ-amylase, acetylcholinesterase, butyrylcholinesterase, tyrosinase), and cell viability (XTT assay) capacity. Extracts from the beginning of flowering period showed stronger biological activity. It has been determined that the extracts have antioxidant, antibacterial (against Staphylococcus aureus) anticancer activity (on breast cancer cells), and inhibition effects of BChE and alpha-glucosidase. It has been determined that the extracts obtained from H. heterophylum have important pharmacological activities, and the plant exhibits higher activity in the BF period. Hypericum heterophyllum Vent. The activities of the chemicals contained in it against various proteins that are α-gly enzyme (PDB ID: 1R47), AChE enzyme (PDB ID: 4M0E), BChE enzyme (PDB ID: 5NN0), alpha-Amylase (PDB ID: 3BAJ), breast cancer protein (PDB ID: 1A52 and 1JNX), were compared. ADME/T analysis of molecules with high activity was performed.

Individual and combined impact of microplastics and lead acetate on the freshwater shrimp (Caridina fossarum): Biochemical effects and physiological responses

Microplastics and heavy metals pollution is recognised as a major problem affecting aquatic ecosystems. For this reason, this study aims to assess the toxicity of different concentrations of polyethylene microplastics (PE-MPs) (0.0, 500, and 1000 μg L−1) with a mean size of 15–25 μm and lead acetate Pb(C2H3O2)2 (0.0, 2.5, and 5 mg L−1), both individually and in combination, through the exposure of the freshwater grass shrimp, Caridinia fossarum for 15 days, focusing on microplastic interaction with co-occurring contaminants. After being exposed to both contaminants, either individually or in combination, significant alterations in numerous biochemical markers were observed. Specifically, exposure to lead acetate alone resulted in significant changes across ALP, AST, ALT, LDH, GGT, and BChE enzyme activity levels indicating hepatotoxicity and neurotoxicity. Also, Pb exposure led to alterations in total antioxidant capacity, MDA, total lipids, and glycogen contents, signalling the onset of oxidative stress. Exposure to PE-MPs alone led to changes in ALP, LDH, GGT, and BChE enzyme levels, and in MDA, total lipids, and glycogen samples' contents. Remarkably, the study observed increased bioaccumulation of lead acetate in samples treated with the combination, emphasizing the synergistic impact of PE-MPs on the toxicity of lead acetate. This synergy was also evident in AST and ALT enzyme activity levels and MDA contents. This underscores the necessity for measures to address both microplastic pollution and heavy metal contamination, taking into account the synergistic behaviour of MPs in the presence of concurrent contaminants.

Synthesis of dimeric 1,2-benzothiazine 1,1-dioxide scaffolds: molecular structures, Hirshfeld surface analysis, DFT and enzyme inhibition studies.

1,2-Benzothiazines are bioactive compounds with diverse pharmacological properties. We report here the synthesis of a series of dimers containing 1,2-benzothiazine scaffolds as potential pharmacophores. The characterization of compounds was done using analytical techniques such as FT-IR, 1H NMR, and elemental analyses. The molecular structures of the compounds (5-8) were confirmed by X-ray crystallography. The molecular interactions in compounds (5-8) were determined by Hirshfeld Surface Analysis (HSA). Density functional theory (DFT) investigations were carried out to calculate vibrational properties, NMR behaviour, dipole moments, molecular electrostatic potential (MEP), frontier molecular orbital (FMO), natural bonding orbital (NBO) analysis and global reactivity descriptors. The global reactivity descriptors indicated the charge transfer reactions and stabilized as follows: 8 > 7 > 6 > 5. In FMO analysis a substantial HOMO-LUMO gap, ranging from 4.43 to 5.12 eV, with high LUMO values was observed for all compounds, while the highest value for linear polarizability was found in compound 8. The in vitro and in silico studies confirm that compound 8 is more active toward AChE and BChE enzymes.

LC–MS/MS phytochemical profiling, antioxidant activity, and enzyme inhibitory of Potentilla reptans L. root: Computational studies and experimental validation

This study attends to evaluate the phytochemical, antioxidant capacity and enzyme inhibition effects of different solvent of Potentilla reptans L. (P. reptans) root extracts (ethyl acetate fraction and methanolic extract) from Iran. The extracts were probed for the total phenolic and flavonoid content. The phytochemical profile was determined using an ultra-high performance liquid chromatography (LC)–tandem mass spectrometry (MS/MS) technique. The DPPH, FRAP, CUPRAC, ABTS, metal chelating, and phosphomolybdenum assays were used to evaluate antioxidant activity. Furthermore, in silico molecular docking and ADMET analysis were carried out on their identified compounds to predict the compounds’ pharmacokinetic indicators and toxicity. The results exhibited that the ethyl acetate fraction has higher levels of total phenolics (120.87 ± 0.63 mg GAE/g) and flavonoids (2.47 ± 0.02 mg RE/g) contents compared to the methanol extract (120.87 ± 0.63 mg GAE/g and 1.33 ± 0.07 mg RE/g, respectively). Moreover, antioxidant assays revealed that ethyl acetate fraction demonstrated higher radical scavenging (DPPH and ABTS) and reducing abilities (FRAP and CUPRAC) than the methanol extract. While, the methanol extract exhibited a stronger chelating ability (22.29 mg EDTAE/g) compared to the ethyl acetate fraction (19.34 mg EDTAE/g). LC/MS analysis exerted 18 compounds in the ethyl acetate fraction and 20 compounds in the methanol extract, including phenolic acids, proanthocyanidins and their derivatives. However, the most of compounds were similar in the both of them. In AChE, BChE, and amylase enzyme inhibition assays, the methanolic extract exhibited higher activity compared with the ethyl acetate fraction. While, the both of them showed similar inhibitory abilities in the tyrosinase inhibition test, but, no significant activity against glucosidase. Based on the results of phytochemical, biological, and computational studies, P. reptans root can be regarded as a potential source of ingredients for the innovative pharmaceutical and nutraceutical applications.

Bioactive sulfonyl hydrazones with indole scaffold, characterization, adme properties, molecular docking studies and investigation of inhibition on choline esterase enzymes for the diagnosis of Alzheimer’s disease

AbstractBackgroundAlzheimer’s disease (AD) is a progressive and neurodegenerative disease that is primarily seen in the elderly population and is clinically characterized by memory and cognitive impairment. This study aimed to find new ChE inhibitors.MethodThe structures of the synthesized compounds were characterized by 1H NMR, 13C NMR and HRMS. The effects of the synthesized hydrazones on acetylcholinesterase and butyrylcholinesterase enzymes were measured using the microplate assay described in the Ellman test, with modifications added by López (2002).ResultAccording to the results, all the synthesized compounds inhibited AChE and BChE enzymes. When the IC50 values were compared, the compounds with indole scaffold and donepezil fragment showed potent inhibitory activity on the AChE enzyme. In addition, the predictive properties of all compounds in terms of drug similarity were scanned using five Lipinski rules and ADME. Also, to evaluate the binding interactions between the hydrazone compounds and enzymes, molecular docking studies were performed and the compounds with the best inhibition effect were tested. Promisingly, the compound 3d showed good permeability in the PAMPA‐BBB model and high in vitro antioxidant activity.ConclusionBoth in vitro and in silico results showed that two compounds could act as promising inhibitors of AChE and the data provided the way to guide future studies.FundingThis research was funded by the Bulgarian National Science Fund (Grant KP‐06‐Н63/11 14.12.2022).

New Imidazo[1,2-a]pyridin-2-yl Derivatives as AChE, BChE, and LOX Inhibitors; Design, Synthesis, and Biological Evaluation

Background: Inhibition of cholinesterase enzyme has been recognized as an important target in the symptomatic treatment of Alzheimer’s disease. Objective: In the current work, a series of new N-(4-(imidazo[1,2-a]pyridin-2-yl)phenyl)cinnamamide derivatives were synthesized and their inhibitory activities against acetyl cholinesterase, butrylcholines terase, and Lipoxygenase were evaluated. Methods: The target compounds were synthesized as the literature reported with some modifications. The AChE, BChE, and LOX inhibitory activities of the synthesized compounds were evaluated using in vitro methods. The docking and kinetic studies were performed for the most potent compounds to evaluate the inhibition mechanism. Results: The structural elucidation of the synthesized imidazo-pyridine derivatives was performed by different spectroscopic techniques including IR, NMR, and Mass. Most of the synthesized compounds demonstrated good AChE, BChE, and LOX inhibitory activities. The most active AChE, BChE, and sLOX-1 inhibitors were found for compounds 4a, 4g, and 4l, respectively. The docking study also revealed that the three compounds, 4a, 4g, and 4l, have important binding interactions with the AChE, BChE, and sLOX-1 enzyme active sites, respectively. Conclusion: The results of current study shows imidazo[1,2-a]pyridine derivatives have potential for development of novel drug candidate for AD as AChE, BChE and sLOX-1 inhibitors.