Enzyme Inhibitory Activity Research Articles

Comparative study on physicochemical properties and hypoglycemic activities of intracellular and extracellular polysaccharides from submerged fermentation of Morchella esculenta

The structural characteristic, physicochemical properties and structure-hypoglycemic activity relationship of intracellular (IPS) and extracellular (EPS) from submerged fermentation of Morchella esculenta were systematically compared and assessed. Both IPS and EPS were neutral, with a triple-helical conformation, and composed of galactose, glucose and mannose monosaccharides in different molar ratios. The molecular weight and particle size of IPS were higher than those of EPS. FTIR and SEM showed that the main functional group absorption peak intensity, glycosidic bond type and surface morphology of the two polysaccharides differed. Analysis of rheological and thermal properties revealed that the viscosity of IPS was higher than that of EPS, while thermal stability of EPS was greater than that of IPS. Hypoglycemic activity analysis in vitro showed that both IPS and EPS were non-competitive inhibitors of α-amylase and α-glucosidase. EPS showed strong digestive enzyme inhibitory activity due to its higher sulphate content and molar ratio of galactose, lower Mw and particle size. Meanwhile, with its higher Mw and apparent viscosity, IPS showed stronger glucose adsorption capacity and glucose diffusion retardation. These results indicate that IPS and EPS differed considerably in structure and physicochemical properties, which ultimately led to differences in hypoglycemic activity. These results not only suggested that IPS and EPS has the potential to be functional foods or hypoglycemic drugs, but also provided a new target for the prevention and treatment of diabetes with natural polysaccharides.

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.

Phytochemical profile, bioactivity, and molecular docking studies of natural edible mushrooms grown in Tokat and Sivas provinces of Turkey.

Mushrooms have been essential to the human diet because they contain balanced chemical components and some biologically active substances. In this work, we investigated the phenolics, essential oils, metal contents, antioxidant, antibacterial, DNA protective, and enzyme inhibition activities for Clitocybe geotropa, Ramaria aurea, Rhizopogon luteolus (RL), Russula delica (RD), Verpa bohemica, and Marasmius oreades mushrooms. Results exhibited a higher content for citric and succinic acids in all tested kinds. Further, we detected a high content of cis-9-oleic acid, linoleate, and cis-11-eicosanoate. All mushroom species contain a significant percentage of both Cu and Zn. Moreover, RL and RD recorded the highest phenolic and flavonoid contents. Furthermore, all samples showed standard to good antioxidant activity, and the same is true for the antibacterial and DNA protective activities. Enzyme inhibition activity was generally high and significantly higher against the urease than the thiourea. We applied molecular docking between the highest phenolic molecules with the urease to determine the mushroom extracts' high inhibition mechanism. In conclusion, all mushroom species revealed a variety in chemical content that is probably related to their multi-bioactivity.

Bioactive, Pro-Apoptotic-Angiotensin Converting Enzyme Inhibitor Effects and Properties of Ultrasound-Treated Traditional Poppy Vinegar Using the Response Surface Methodology Model.

Poppy vinegar with functional properties is a fermented product. This study evaluated traditionally produced poppy vinegar. The study was conducted on poppy vinegar to determine the maximum increase in angiotensin converting enzyme (ACE) inhibitory activity %, total phenolic content (TPC), and radical scavenging activity (DPPH) of the vinegar at different combinations of ultrasound treatment duration (2-14 min) and amplitude (40-100%). The optimal parameters obtained using the response surface methodologies (RSM) were the duration of the ultrasound of 5.5 min and the amplitude of the ultrasound at 57%. When the DPPH values, ACE inhibition %, and TPC and DPPH values obtained with the RSM model were compared with the experimental values, the difference was 9.80, 3.0, and 4.6%, respectively, showing good agreement between actual and predicted values. The higher ultrasound intensities and longer treatment times had a significant effect on antioxidant activity. Poppy vinegar samples significantly induced the apoptosis of lung cancer cells, particularly those stored for 6 and 12 months. The amounts of protocatechuic acid, gallic acid, neohesperidin, hydroxybenzoic acid, resveratrol, rutin, trans-cinnamic acid, quercetin, and flavon in poppy vinegar were determined, which decreased significantly as storage time increased. TPC and TFC were determined to be 90.39 mg of GAE/100 mL and 29.86 mg of TEAC/mL, respectively, and there was no significant change in these bioactive compounds after 6 months of storage. The highest value of ACE inhibitory activity was found at the beginning of the storage period. The present study was the first study to examine the bioactive components, ACE inhibition activity, pro-apoptotic activities, and phenolic composition of traditionally produced ultrasound-treated poppy vinegar during storage. The control of production parameters and the design of ideal poppy vinegar fermentation processes could benefit from this research.

Chemical composition, antioxidant activity, enzyme inhibitory effects, and network pharmacology analysis of essential oil from Bulbophyllum kwangtungense Schltr.

The present study investigates the chemical composition of the essential oil (EO) from Bulbophyllum kwangtungense Schltr., evaluates its antioxidant, enzyme inhibitory activities, and analyzes its therapeutic mechanisms against oxidative damage through network pharmacology. The main components identified were n-hexadecanoic acid (9.95 %), linalool (9.17 %), 1-hexanol (5.16 %), pentadecanoic acid (4.66 %), (Z)-3-hexen-1-ol (3.39 %), phytol (2.67 %), linoleic acid (2.49 %), 1-hexadecanol (2.39 %), α-curcumene (2.28 %). The 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS), 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) free radical scavenging capacity was characterized by IC50 values of 0.43 ± 0.08 mg/mL and 3.87 ± 1.26 mg/mL. The ferric reducing antioxidant power (FRAP) antioxidant value (Trolox equivalent antioxidant concentration) was 116.49 ± 0.26 μM/g. The EO exhibited anti-β-lactamase activity with an IC50 of 229.4 ± 18.7 μg/mL. The anti-acetylcholinesterase activity was 18.10 ± 2.71% at the 500 μg/mL concentration. The network pharmacology analysis was conducted to reveal potential targets and pathways of oxidative damage involved in the therapeutic effects of our EO.

Ziziphus mauritiana Lam. Bark and Leaves: Extraction, Phytochemical Composition, In Vitro Bioassays and In Silico Studies.

In this work, homogenizer-assisted extraction (HAE) and maceration (MAE) were applied on leaves and bark of Ziziphus mauritiana using water and methanol (MeOH) as solvents. HAE and MAE extracts were compared through liquid chromatography coupled with mass spectrometry (LC-MS) and evaluating the antioxidant activity, and enzyme inhibition against acetylcholinesterase (AChE), butrylcholinesterase (BChE), tyrosinase, α-amylase, and α-glucosidase. Considering the phytochemical contents and the bioassays results, the HAE extracts resulted favorably with larger content of phenolics and higher antioxidant activity. The MeOH extracts displayed the highest α-amylase inhibitory activity, with HAE MeOH leaf extract leading at 0.78 mmol acarbose equivalent (ACAE)/g. In conclusion, the study highlights that HAE can increase the extraction of phenolic and flavonoid from Z. mauritiana plant materials compared to maceration. Further research could explore the potential therapeutic applications of Z. mauritiana extracts, especially HAE MeOH leaf extracts, for their notable antioxidant and enzyme inhibitory activities, facilitating the way for the development of novel pharmaceutical interventions.

Evaluation of Antioxidant Potential, Enzyme Inhibition, and Chemical Profiling Through Mass Spectrometry on Bark Extract of Berberis aristata

Berberis aristata, a plant from the Berberidaceae family, is renowned for its medicinal properties. The presence of bioactive metabolites in its bark underscores its importance in traditional medicine and pharmacology. This study primarily focuses on the biological activities of the plant bark extract, specifically its antioxidant properties and alpha-glucosidase inhibition. In addition to these activities, mass spectrometry-based compound annotation was conducted to explore the metabolites present in the plant bark extract. In this study, the bark samples were collected and extracted using the cold percolation method with methanol. Subsequently, an ethyl acetate fraction was obtained from the methanol extract using a separating funnel. The methanol extract of the bark showed a total phenolic content (TPC) of 70.056 ± 2.52 mg GAE/g and a total flavonoid content (TFC) of 11.89 ± 0.16 mg QE/g. To determine the antioxidant activity of the samples, a DPPH assay was used. The ethyl acetate fraction of the bark showed potent antioxidant activity with an IC50 value of 188.93 ± 8.35 μg/mL, while the methanol extract of the bark showed radical scavenging activity with an IC50 value of 242.89 ± 4.62 μg/mL. In terms of alpha-glucosidase inhibition, the methanol extract of the bark had low enzyme inhibition activity, but the ethyl acetate fraction exhibited potential inhibition with an IC50 value of 112.99 ± 10.28 µg/mL. These results indicate that the plant bark extract is rich in phenolic content compared to flavonoid content. Additionally, the ethyl acetate fraction of the plant bark exhibits potent radical scavenging activity and inhibition of the digestive enzyme alpha-glucosidase. Mass spectrometric-based identification of metabolites revealed that the methanol extract of the bark contains compounds such as Palmatin, columbamine, and berberal. The presence of these metabolites further supports the medicinal use of this plant bark. These findings enhance the plant's potential in the drug discovery process in the future.

Bioactive profiling of two varieties of Indian legumes: adzuki and mung beans

SummaryNutritional benefits of legumes make them an important part of sustainable diets. They are rich not only in dietary fibres, proteins, and micronutrients but also in the bioactive compounds that can exhibit various biological activities. In the present study, we aimed to investigate the nutritional analysis, phytochemical composition, and in vitro anti‐obesity activity of two varieties of legumes indigenous to India namely, adzuki beans (Vigna angularis) and mung beans (Vigna radiata). GC–MS, UHPLC‐QTOF‐MS, ICP‐MS analyses were done for bioactive compounds, fatty acids, macro‐elements, micro‐elements, protein, and non‐proteinogenic amino acids. GC–MS analysis showed that the major constituents identified were hydrocarbons, fatty acids, and terpenes, while the presence of various secondary metabolites, macro‐ and micro‐nutrients were detected using UHPLC‐QTOF‐MS and ICP‐MS, respectively. FAME analysis revealed a higher concentration of linoleic acid in adzuki beans, which is nutritionally beneficial for human consumption. Amino acid profiling revealed the presence of essential, non‐essential, and non‐proteinogenic amino acids. Further, adzuki beans and mung beans were screened for cytotoxicity on 3T3‐cell line and it was observed that adzuki beans were less cytotoxic as compared to mung beans. Adzuki beans showed higher HMG‐Co‐A reductase enzyme inhibition activity (60%) as compared to mung beans (2.79%). The results indicate that these two legumes are a very good source of bioactive metabolites and can be developed into novel cholesterol‐lowering and anti‐obesity functional foods.

Chemical characterization and angiotensin-I converting enzyme inhibitory activity of Indonesian stinky beans

The chemical composition of four Indonesian stinky beans has been explored. Those bean are Petai (Parkia speciosa), Lamtoro Gung (Leucaena leucochepala ssp. Glabrata (Rose) S. Zarate), Jengkol (Pithecellobium jiringa) and Kabau (Archidendron bubalinum). This exploration belongs to the local food utilization research theme of functional food sources. Those beans have a unique flavour and usually lead to foul stools, sweat, urine or mouth odour. Their intense flavour may be due to the content of amino acids. High hydrophobic and negative charge hydrophilic amino acids are crucial in preventing hypertension through inhibition of angiotensin I-converting enzyme (ACE) activity. This study evaluated the chemical properties of beans and its angiotensin I-converting enzyme inhibitory (ACE-I) peptides. The amino acid profile was determined as preliminary data to ensure the content of hydrophobic and negative charge hydrophilic amino acids. Their ability to inhibit ACE was studied to represent an antihypertensive effect. In vitro gastrointestinal digestion was applied to obtain more small molecular peptides and evaluate their ACE-I activity after digestion. Petai has the highest glutamic acid (20.90 g/100 g protein d.b.), lysine (13.31 g/100 g protein d.b.), arginine (11.76 g/100 g protein d.b.), leucine (10.98 g/100 g protein d.b.), and aspartic acid (10.72 g/100 g protein d.b.). Fresh Jengkol has the highest ACE-I activity (67.59%). Subsequential digestion by pepsin and pancreatin improves the ACE-I activity, and Kabau had the highest (79.87%). Based on the results, Indonesian stinky beans can prevent hypertension by inhibiting ACE activity and being used as a protein source alternative

Phytochemical Characterization and Bioactivity of Extracts from Different Fruit Parts of Opuntia leucotricha DC.: A Comparison between a Conventional Organic Solvent and Green Natural Deep Eutectic Solvents

The objective of this study was to analyze the chemical profile of extracts from different fruit parts of the perennial arborescent cactus Opuntia leucotricha by applying ultra-high-performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HRMS) and to evaluate their biological properties (antioxidant and enzyme inhibitory capacities). Extracts were obtained from the fruit pulp (without or with seeds), seeds, and peel by ultrasound-assisted extraction (UAE) using the conventional solvent methanol 50% and two Natural Deep Eutectic Solvents (NADESs) (glycerol:urea, 1:1 and citric acid:sorbitol, 1:2). A total of 33 compounds were identified, including phenolics, fatty acids, and others. Phenolic acids were the most abundant class of phenolics identified in all fruit parts, with the highest concentration observed in the methanol extracts from peel (593.02 µg/gDW), followed by seed-containing pulp (69.03 µg/gDW), pulp (57.83 µg/gDW), and seeds (39.97 µg/gDW). The second most effective extractant was NADES 1 (glycerol:urea, 1:1), which was also successful in extracting compounds with antioxidant capacity. Overall, the extracts demonstrated considerable enzyme inhibitory activities, with the greatest effects observed against α-amylase and α-glucosidase. The results indicate that O. leucotricha fruits could be a promising source of bioactive compounds, and NADES a viable alternative to organic solvents for their industrial exploitation.

Assessment of the Effect of Berberine on Metalloprotease Enzymes Inhibition and Antioxidant Activity: Possible Application in Skin Aging

Assessment of the Effect of Berberine on Metalloprotease Enzymes Inhibition and Antioxidant Activity: Possible Application in Skin Aging

Protein Hydrolysates from Salmon Heads and Cape Hake By-Products: Comparing Enzymatic Method with Subcritical Water Extraction on Bioactivity Properties.

Fish by-products can be converted into high-value-added products like fish protein hydrolysates (FPHs), which have high nutritional value and are rich in bioactive peptides with health benefits. This study aims to characterise FPHs derived from salmon heads (HPSs) and Cape hake trimmings (HPHs) using Alcalase for enzymatic hydrolysis and Subcritical Water Hydrolysis (SWH) as an alternative method. All hydrolysates demonstrated high protein content (70.4-88.7%), with the degree of hydrolysis (DH) ranging from 10.7 to 36.4%. The peptide profile of FPHs indicated the breakdown of proteins into small peptides. HPSs showed higher levels of glycine and proline, while HPHs had higher concentrations of glutamic acid, leucine, threonine, and phenylalanine. Similar elemental profiles were observed in both HPHs and HPSs, and the levels of Cd, Pb, and Hg were well below the legislated limits. Hydrolysates do not have a negative effect on cell metabolism and contribute to cell growth. HPSs and HPHs exhibited high 2,2'-azino-bis(3 ethylbenzthiazoline-6)-sulfonic acid (ABTS) radical scavenging activity, Cu2+ and Fe2+ chelating activities, and angiotensin-converting enzyme (ACE) inhibitory activity, with HPHs generally displaying higher activities. The α-amylase inhibition of both FPHs was relatively low. These results indicate that HPHs are a promising natural source of nutritional compounds and bioactive peptides, making them potential candidates for use as an ingredient in new food products or nutraceuticals. SWH at 250 °C is a viable alternative to enzymatic methods for producing FPHs from salmon heads with high antioxidant and chelating properties.

Fermentation of Rice, Oat, and Wheat Flour by Pure Cultures of Common Starter Lactic Acid Bacteria: Growth Dynamics, Sensory Evaluation, and Functional Properties.

Recent consumer demand for non-dairy alternatives has forced many manufacturers to turn their attention to cereal-based non-alcoholic fermented products. In contrast to fermented dairy products, there is no defined and standardized starter culture for manufacturing cereal-based products. Since spontaneous fermentation is rarely suitable for large-scale commercial production, it is not surprising that manufacturers have started to adopt centuries-known dairy starters based on lactic acid bacteria (LABs) for the fermentation of cereals. However, little is known about the fermentation processes of cereals with these starters. In this study, we combined various analytical tools in order to understand how the most common starter cultures of LABs affect the most common types of cereals during fermentation. Specifically, 3% suspensions of rice, oat, and wheat flour were fermented by the pure cultures of 16 LAB strains belonging to five LAB species-Lacticaseibacillus paracasei, Lactobacillus delbrueckii, Lactobacillus helveticus, Streptococcus thermophilus, and Lactococcus lactis. The fermentation process was described in terms of culture growth and changes in the pH, reducing sugars, starch, free proteins, and free phenolic compounds. The organoleptic and rheological features of the obtained fermented products were characterized, and their functional properties, such as their antioxidant capacity and angiotensin-converting enzyme inhibitory activity, were determined.

Synthesis of 1,2,3-triazole functionalized derivatives of metronidazole as potent inhibitors of urease: Synthesis via click chemistry, in vitro urease inhibition, kinetics and molecular docking studies

Current study is based on multistep synthesis of sixteen new 1,2,3-triazole functionalized derivatives of metronidazole drug 3–18 by using a Cu(I)-catalysed 1,3-dipolar azide-alkyne cycloaddition (CuAAC) reaction via a click chemistry approach. All the compounds were purified by using conventional silica gel column chromatography with isocratic eluent. Their structures were confirmed by using various spectroscopic techniques including UV, IR, LR and HR MS, 1H-, 13CNMR , and 2D-NMR spectroscopy. The library of 1,2,3-triazole derivatives of metronidazole 3–18 was evaluated for urease inhibitory activity, and cytotoxicity against normal cells. Compound 8 (IC50= 6.8 ± 0.8 µM) was found to be the most potent urease inhibitor, while acetohydroxamic acid (IC50 = 20.3 ± 0.4 µM) was used as experimental standard. Compounds 5 (IC50 = 7.9 ± 0.9 µM), 6 (IC50 = 9.5 ± 0.2 µM), 7 (IC50 = 8.5 ± 1.0 µM), 10 (IC50 = 9.3 ± 1.1 µM), and 18 (IC50 = 7.2 ± 0.6 µM) were also found to be potent inhibitors of urease. Parent drug metronidazole also showed a potent urease enzyme inhibitory activity with IC50= 10.54 ± 0.8 µM. All compounds were found to be non-cytotoxic against the human fibroblast (B.J.) cell line. Molecular docking and kinetic studies were performed for compounds 5–8, 10, and 18 which showed that these compounds are competitive inhibitors of urease enzyme inhibition. Urease inhibition is a therapeutic approach to help in the treatment of peptic ulcers, caused by ureolytic bacteria. The initial findings presented herein therefore, deserve further studies.

Probing N-substituted 4-(5-mercapto-4-ethyl-4H-1,2,4-triazol-3-yl)-N-phenylpiperdine-1-carboxamides as potent 15-LOX inhibitors supported with ADME, DFT calculations and molecular docking studies

In our continuous efforts to find out leads against the enzyme 15-lipoxygenase (15-LOX), the current study deals with the synthesis of a series of new N-alkyl/aralkyl/aryl derivatives of 2-(4-ethyl-5-(1-phenylcarbamoyl)piperidine-4H-1,2,4-triazol-3-ylthio)methylacetamide (7a-n) with anti-LOX activities. The synthesis was started by reacting phenylisocyanate with isonipecotate that sequentially converted into N-substituted ester (1), hydrazide (2), semicarbazide (3) and N-ethylated 5-(1-phenylcarbamoyl)piperidine-1,2,4-triazole (4). The final compounds, 7a-n, were obtained by reacting 4 with various N-alkyl/aralkyl/aryl electrophiles. Both the intermediates and target compounds were characterized by FTIR, 1H, 13C NMR spectroscopy, EI-MS and HR-EI-MS spectrometry and screened against soybean 15-LOX by chemiluminescence method. The eight compounds 7e, 7j, 7h, 7a, 7g, 7b, 7n, 7c showed potent inhibitory activities against 15-LOX with values ranging from IC50 0.36 ± 0.15 μM (7e) to IC50 6.75 ± 0.17 μM (7c) compared with the reference quercetin (IC50 4.86 ± 0.14 μM) and baicalein (IC50 2.24 ± 0.13 μM). Two analogues (7l, 7f) had significantly outstanding inhibitory potential with IC50 values 12.15 ± 0.23 μM and 15.54 ± 0.26 μM, whereas, the derivatives 7i, and 7d displayed IC50 values of 21.56 ± 0.27 μM, 23.59 ± 0.24 μM and the compounds 7k, 7m were found inactive. All analogues exhibited blood mononuclear cells (MNCs) viability >75 % at 0.25 mM concentration as determined by MTT method. Calculated pharmacokinetic properties projected good lipophilicity, bioavailability and drug-likeness properties and did not violate Lipinski's/Veber rule. Molecular docking studies revealed lower binding free energies of all the derivatives than the reference compounds. The binding free energies were −9.8 kcal/mol, −9.70 k/mol and −9.20 kcal/mol for 7j, 7h and 7e, respectively, compared with the standard quercetin (−8.47 kcal/mol) and baicalein (−8.98 kcal/mol). The docked ligands formed hydrogen bonds with the amino acid residues Gln598 (7e), Arg260, Val 126 (7h), Gln762, Gln574, Thr443, Arg580 (7j) while other hydrophobic interactions observed therein further stabilized the complexes. The results of density functional theory (DFT) revealed that analogues with more stabilized lower unoccupied molecular orbital (LUMO) had significant enzyme inhibitory activity. The data collectively supports these molecules as leads against 15-LOX and demand further investigations as anti-inflammatory agents.

Design, Synthesis, and Biological Activity of Silicon-Containing Carboxamide Fungicides.

Bioisosteric silicon replacement has proven to be a valuable strategy in the design of bioactive molecules for crop protection and drug development. Twenty-one novel carboxamides possessing a silicon-containing biphenyl moiety were synthesized and tested for their antifungal activity and succinate dehydrogenase (SDH) enzymatic inhibitory activity. Among these novel succinate dehydrogenase inhibitors (SDHIs), compounds 3a, 3e, 4l, and 4o possessing appropriate clog P and topological polar surface area values showed excellent inhibitory effects against Rhizoctonia solani, Sclerotinia sclerotiorum, Botrytis cinerea, and Fusarium graminearum at 10 mg/L in vitro, and the EC50 values of 4l and 4o were 0.52 and 0.16 mg/L against R. solani and 0.066 and 0.054 mg/L against S. sclerotiorum, respectively, which were superior to those of Boscalid. Moreover, compound 3a demonstrated superior SDH enzymatic inhibitory activity (IC50 = 8.70 mg/L), exhibiting 2.54-fold the potency of Boscalid (IC50 = 22.09 mg/L). Docking results and scanning electron microscope experiments revealed similar mode of action between compound 3a and Boscalid. The new silicon-containing carboxamide 3a is a promising SDHI candidate that deserves further investigation.

Investigation of the chemical composition, antioxidant, and enzyme inhibitory activities of Ononis natrix subsp. natrix, performance of in silico analyses of its major compounds

In this study, phytochemical composition, antioxidant, anti-Alzheimer, anti-diabetic, tyrosinase activities and in silico analyses of methanol, ethyl acetate and water extracts obtained from the aerial parts of Ononis natrix subsp. natrix, which is naturally distributed in the flora of Mediterranean area, were performed. The extracts were first analyzed for their phytochemical composition using quantitative chromatographic techniques. As a result of spectrophotometric analyses (Agilent Technologies 1260 Infinity liquid chromatography system with 6420 Triple Quad mass spectrometer), it was determined that the methanol extract was the richest in terms of total phenolics (74.60 mg GAEs/g dry weight), while the water extract was found to be richest in terms of total flavonoids (27.88 mg REs/g dry weight). As a result of quantitative phytochemical analyses, taxifolin, hyperoside, eriodictiol and quercetin were found to be present in high concentrations. As a result of quantitative phytochemical analyses, taxifolin, hyperoside, eriodictyol, and quercetin were found to be present in high concentrations. The methanol extract displayed higher activity in all test systems except for DPPH radical scavenging activity. The results from the phosphomolybdenum, ABTS radical scavenging, CUPRAC, FRAP, and metal chelating tests for the methanol extract were: 1.71, 1.07, 1.02 mg, 0.91, and 1.47 mg /ml, respectively. When the AChE, BChE and α-glucosidase inhibitory activity tests were evaluated in terms of IC50, the methanol extract showed higher activity with IC50 values of 1.02, 1.70 and 1.02 mg/ml, respectively. In contrast, the ethyl acetate extract showed higher activity in the tyrosinase and α-amylase tests, with IC50 values of 1.42 and 1.78 mg/ml, respectively. It was found that there was a strong correlation between the total phenolic and flavonoid contents of the extracts and their antioxidant and enzyme inhibitor activities. The study also conducted in silico molecular docking, MM/GBSA, drug-likeness, and ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) analyses to describe the pharmacokinetic and pharmacodynamic properties of bioactive compounds with potential pharmacological action present in O. natrix subsp. natrix extracts. The compounds studied were eriodictyol, hyperoside, quercetin, and taxifolin. Researchers have found that, based on molecular docking, MM/GBSA, and key interactions within the enzyme active sites, hyperoside may inhibit α-amylase and BChE, eriodictyol may inhibit α-glucosidase and AChE, and both hyperoside and eriodictyol may inhibit tyrosinase. The presented data on antioxidant and enzyme inhibitory activity, along with in silico studies, represent the first recorded findings in the literature.

Discovery, Optimization, and Biological Evaluation of Novel Pyrazol-5-yl-phenoxybenzamide Derivatives as Potent Succinate Dehydrogenase Inhibitors.

The diphenyl ether molecular pharmacophore has played a significant role in the development of fungicidal compounds. In this study, a variety of pyrazol-5-yl-phenoxybenzamide derivatives were synthesized and evaluated for their potential to act as succinate dehydrogenase inhibitors (SDHIs). The bioassay results indicate certain compounds to display a remarkable and broad-spectrum in their antifungal activities. Notably, compound 12x exhibited significant in vitro activities against Valsa mali, Gaeumannomyces graminis, and Botrytis cinerea, with EC50 values of 0.52, 1.46, and 3.42 mg/L, respectively. These values were lower or comparable to those of Fluxapyroxad (EC50 = 12.5, 1.93, and 8.33 mg/L, respectively). Additionally, compound 12x showed promising antifungal activities against Sclerotinia sclerotiorum (EC50 = 0.82 mg/L) and Rhizoctonia solani (EC50 = 1.86 mg/L), albeit lower than Fluxapyroxad (EC50 = 0.23 and 0.62 mg/L). Further in vivo experiments demonstrated compound 12x to possess effective protective antifungal activities against V. mali and S. sclerotiorum at a concentration of 100 mg/L, with inhibition rates of 66.7 and 89.3%, respectively. In comparison, Fluxapyroxad showed inhibition rates of 29.2 and 96.4% against V. mali and S. sclerotiorum, respectively. Molecular docking analysis revealed that compound 12x interacts with SDH through hydrogen bonding, π-cation, and π-π interactions, providing insights into the probable mechanism of action. Furthermore, compound 12x exhibited greater binding energy and SDH enzyme inhibitory activity than Fluxapyroxad (ΔGcal = -46.8 kcal/mol, IC50 = 1.22 mg/L, compared to ΔGcal = -41.1 kcal/mol, IC50 = 8.32 mg/L). Collectively, our results suggest that compound 12x could serve as a promising fungicidal lead compound for the development of more potent SDHIs for crop protection.

A Machine Learning Approach to Evaluating the Impact of Natural Oils on Alzheimer’s Disease Progression

Alzheimer’s Disease is among the major chronic neurodegenerative diseases that affects more than 50 million people worldwide. This disease irreversibly destroys memory, cognition, and the overall daily activities which occur mainly among the elderly. Few drugs are approved for Alzheimer’s Disease management despite its high prevalence. To date, the available drugs in the market cannot reverse the damage of neurons caused by the disease leading to the exacerbation of symptoms and possibly death. Medicinal plants are considered a rich source of chemical constituents and have been contributing to modern drug discovery in many therapeutic areas including cancer, infectious, cardiovascular, neurodegenerative and Central Nervous System (CNS) diseases. Moreover, essential oils that are extracted from plant organs have been reported for a wide array of biological activities, and their roles as antioxidants, antiaging, cytotoxic, anti-inflammatory, antimicrobial, and enzyme inhibitory activities. This article highlights the promising potential of plants’ essential oils in the discovery of novel therapeutic options for Alzheimer’s Disease and halting its progression. In this article, 428 compounds were reported from the essential oils isolated from 21 plants. A comparative study is carried out by employing a variety of machine learning techniques, validation, and evaluation metrics, to predict essential oils’ efficacy against Alzheimer’s Disease progression. Extensive experiments on essential oil data suggest that a prediction accuracy of up to 82% can be achieved given the proper data preprocessing, feature selection, and model configuration steps. This study underscores the potential of integrating machine learning with natural product research to prioritize and expedite the identification of bioactive essential oils that could lead to effective therapeutic interventions for Alzheimer’s Disease. Further exploration and optimization of machine learning techniques could provide a robust platform for drug discovery and development, facilitating faster and more efficient screening of potential treatments.

Green extraction, chemical profile and biological activity of waste products from the olive oil industry: From waste to wealth

Olive oil is the most used vegetable oil for human consumption and its production represents an important economic sector, especially in Mediterranean countries. Olive trees are grown in more than 40 countries around the world on over 10 million hectares. The milling industry generates large quantities of liquid and solid residues, the disposal of which requires sophisticated and rather expensive procedures, given the polluting characteristics of the processing products. Since a considerable measure of olive-derived biomass is generated each year, it could be used as a potential source of bioactive compounds. This work evaluates the possibility of recovering natural antioxidants from by-products of the olive oil mill, through the optimization of extraction processes with green approaches. In the present work, through HPLC-PDA analysis with a validated method, it was possible to characterize a chemical profile of the extracts obtained through an optimized (DoE) and green approach. The waste products of the olive oil companies represent the samples considered in this work, and are derived from the pomace and the washing water of 2-phases, 2.5-phases, and 3-phase extra virgin olive oil (EVO) production plants. The optimized extraction methodology, starting from the 2.5-phase olive pomace, proved to be satisfactory in terms of efficiency by evaluating the effect of parameters such as extraction time and process temperature. The application of this methodology to other types of pomace and agro-industrial by-products has highlighted excellent results in terms of extraction yield, demonstrating the validity of this procedure as also suitable for other solid residues coming from the olive oil mill. Regarding the treatment in vegetation water, the developed protocol allowed the chromatographic profile of the analytes extracted from this matrix to be evaluated, leading to satisfactory results in terms of quantitative yields. Samples of these extracts are also subjected to biological tests in order to evaluate their antioxidant and enzyme inhibition activities.