Antiglycation Activity Research Articles

Integration of in vitro and in-silico analysis of Caulerpa racemosa against antioxidant, antidiabetic, and anticancer activities

Marine algae are found to be excellent in their nutritional and potential therapeutic properties. This study explores the antidiabetic and anticancer potential of fractionated polyphenolic extract of Caulerpa racemosa, green macroalgae. Crude polyphenolic extract (CPE) of C. racemosa and its fractions (n-hexane, ethyl acetate, chloroform, and distilled water) were tested for its total phenol and flavonoid contents and antioxidant potential. The ethyl acetate fraction was subjected to gas chromatography/mass spectrometry (GC/MS). The in vitro antidiabetic activity was assessed by alpha-amylase, glucosidase inhibition and anti-glycation assays. Also, in-silico studies were conducted to test the binding affinities between caulerpin with alpha-glucosidase enzyme and estrogen receptor (ER) active sites. Each fraction was tested for its in vitroin vitroanticancer activity by CellTiter-Glo and MTT cell proliferation assays. The total phenolic and flavonoid contents and the antioxidant potential of the crude extract were observed to be dose dependent. The GC/MS analysis of the ethyl acetate fraction yielded 47 peaks, whereas n-hexadecanoic acid and hexadecanoic acid methyl ester showed the highest compatibility percentages of 99% and 96%, respectively. The CPE exhibited a higher potential in both alpha-amylase inhibitory and anti-glycation activities. The ethyl acetate fraction was more effective against alpha-glucosidase inhibition. Molecular docking revealed a high binding affinity between the alpha-glucosidase enzyme and caulerpin and showed high binding affinity toward caulerpin, with H-bond interactions. The in vitro anticancer analyses revealed that chloroform fraction and CPE exhibited moderate activity on the KAIMRC1 cell line. Also, the CPE exhibited high specificity compared to the standard drug in anticancer studies. Our findings evidence the pharmacological potential of the CPE of C. racemosa, and bioactive compounds of the species may be utilized as lead molecules to develop anti-diabetic and anti-cancer drugs.

Inhibitory effects of rooibos (Aspalathus linearis) against reactive carbonyl species and advanced glycation end product formation in a glucose-bovine serum albumin model and cookies.

In thermally processed foods, several heat-induced toxicants are potentially formed due to the Maillard reaction, such as α-dicarbonyls and advanced glycation end products (AGEs). In the present work, we found that the methylglyoxal (MGO)-trapping and antiglycative activities of the herbal tea samples correlated strongly with their total phenolic and flavonoid contents. Among the tested herbal tea samples, rooibos exhibited the strongest MGO-trapping and antiglycative activities against AGEs formation. Aspalathin, orientin and isoorientin were further identified as the major bioactive compounds of rooibos that scavenged MGO to form the corresponding mono-MGO adducts. Moreover, the contents of dicarbonyls and AGEs in the cookie were remarkably reduced by fortification with rooibos. Altogether, our current findings suggested that rooibos might serve as a functional ingredient to reduce intake of dietary reactive carbonyl species (RCS) and AGEs from thermally processed foods, especially bakery products.

2-Mercaptobenzimidazole Based Hydrazone Derivatives as Potential Antioxidant and α-Glucosidase Inhibitors

Background: Schiff bases are organic compounds and play a vital role in making biologically active compounds in various fields of chemistry. It shows antioxidant, antidepressant, antimalarial, anti-inflammatory, antiglycation, and antimicrobial activity. Objective: Our current study is focused on synthesizing thirty-four 2-mercaptobenzimidazole (MBI) based novel hydrazone derivatives (09-42) which were examined for antioxidant free radical scavenging activity via both 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydrogen peroxide (H2O2) assay and explored their alpha-glucosidase inhibitory potential at various concentrations. Methods: Multistep reactions were involved in the synthesis of 2-mercaptobenzimidazole-based hydrazone derivatives. All steps of the reaction were carried out under different conditions through a reflux condenser to get the final target products, and the reaction was monitored regularly in each step through thin layer chromatography (TLC). The antioxidant and α-glucosidase inhibition assay was performed. Results:: Obtained results of antioxidants confirmed that compounds 42 (IC50 = 27.21μg/mL), 36 (IC50 = 27.90μg/mL), 23 (IC50 = 28.10μg/mL) and 35 (IC50 = 45.60μg/mL) possess excellent potential activity compared to standard ascorbic acid having (IC50 = 60.15 μg/mL) in DPPH assay. While in the case of H2O2 three compounds 38 (IC50 = 51.45 μg/mL), 15 (IC50 = 53.50 μg/mL), and 42 (IC50 = 60.42 μg/mL) showed excellent activity as compared to standard Gallic acid having (IC50= 60.67 μg/mL). In the screened compounds against alpha-glucosidase, compound 14 (IC50 = 162 μg/mL) was found to be the most active in the whole series. Another active compound 42 (IC50 = 237μg/mL) possessed moderate inhibitory potency against α-glucosidase enzyme. Conclusion: The different biological activities of these novel compounds may be due to different groups in the main skeleton of 2-mercaptobenzimidazole. Further experimental analysis and assessment of these compounds are important because they may lead to better antioxidants used in foods, cosmetics, and health-related products and act as antidiabetic drug development.

Aspalathin and Other Rooibos Flavonoids Trapped α-Dicarbonyls and Inhibited Formation of Advanced Glycation End Products In Vitro

The excessive dietary intake of simple sugars and abnormal metabolism in certain diseases contribute to the increased production of α-dicarbonyls (α-DCs), such as methylglyoxal (MGO) and glyoxal (GO), the main precursors of the formation of advanced glycation end products (AGEs). AGEs play a vital role, for example, in the development of cardiovascular diseases and diabetes. Aspalathus linearis (Burman f.) R. Dahlgren (known as rooibos tea) exhibits a wide range of activities beneficial for cardio-metabolic health. Thus, the present study aims to investigate unfermented and fermented rooibos extracts and their constituents for the ability to trap MGO and GO. The individual compounds identified in extracts were tested for the capability to inhibit AGEs (with MGO or GO as a glycation agent). Ultra-high-performance liquid chromatography coupled with an electrospray ionization mass spectrometer (UHPLC-ESI-MS) was used to investigate α-DCs' trapping capacities. To evaluate the antiglycation activity, fluorescence measurement was used. The extract from the unfermented rooibos showed a higher ability to capture MGO/GO and inhibit AGE formation than did the extract from fermented rooibos, and this effect was attributed to a higher content of dihydrochalcones. The compounds detected in the extracts, such as aspalathin, nothofagin, vitexin, isovitexin, and eriodictyol, as well as structurally related phloretin and phloroglucinol (formed by the biotransformation of certain flavonoids), trapped MGO, and some also trapped GO. AGE formation was inhibited the most by isovitexin. However, it was the high content of aspalathin and its higher efficiency than that of metformin that determined the antiglycation and trapping properties of green rooibos. Therefore, A. linearis, in addition to other health benefits, could potentially be used as an α-DC trapping agent and AGE inhibitor.

Vanillic Acid Inhibited the Induced Glycation Using In Vitro and In Vivo Models.

Glycation is implicated in the pathophysiology of many diseases, including diabetes, cancer, neurodegenerative diseases, and aging. Several natural and synthetic compounds were investigated for their antiglycation activity. We evaluated the antiglycation effect of vanillic acid (VA) using in vitro and in vivo experimental models. In vitro, bovine serum albumin (BSA) (50 mg/ml) was incubated with glucose (50 mM) with or without VA at 1.0-100 mM for 1 week at 37°C, and then, excitation/emission fluorescence was measured at 370/440 nm to determine glycation inhibition. The cytoprotective effect of VA was evaluated using RAW 264.7 cells incubated with or without VA at 7.8-500 μM along with 100-400 μM of methylglyoxal for 48 hours, and cell viability was determined using the MTT assay. Aminoguanidine (AMG) was used as a positive control in both in vitro and cell culture experiments. In vivo, 52 streptozotocin-induced diabetic rats were randomly assigned to 4 groups and treated with 0, 1.5, 4.5, or 15 mg/kg VA for four weeks. Serum fructosamine and blood glycosylated hemoglobin (HbA1c) were then measured, and advanced glycation end-products (AGEs) were detected in the kidneys and the skin of deboned tails using an immunohistochemistry assay. VA caused a concentration-dependent effect against BSA glycation (IC50 of 45.53 mM vs. 5.09 mM for AMG). VA enhanced cell viability at all concentrations of VA and methylglyoxal. VA did not affect serum fructosamine or blood HbA1c levels, although it markedly decreased AGEs in the kidney in a dose-dependent manner and decreased AGEs in the skin of deboned tail tissues. VA had significant antiglycation activity at cellular and long-term glycation.

Activity‐guided purification and identification of endogenous bioactive peptides from barley sprouts (Hordeum vulgare L.) with diabetes treatment potential

SummaryMetabolic‐associated disorders such as blood pressure and type 2 diabetes (T2D) are some of modern society's widespread problems. While there are many beneficial treatments, the quest for “safe” alternatives using natural products (e.g., cereals) is of great promise, especially plant‐based peptides containing inherently endogenous bioactivities that can provide multiple health‐promoting effects. Here, we aimed to purify and identify potential endogenous peptides of barley sprouts through an activity‐guided process with a potential T2D therapeutical effect. Barley seeds were germinated, and sprouts were fractionated through ultrafiltration followed by RP‐HPLC. All peptide fractions were examined for various bioactivities (α‐glucosidase/DPP4 inhibition, antiglycation, antioxidant and metal chelation activities). LC‐Q‐TOF‐MS/MS was employed for sequence identification of the fraction with the highest activity level. The data demonstrated that fractions with molecular weights lower than 3 kDa were the only ones with antiglycation activities. The RP‐HPLC of the 3 kDa fraction resulted in 11 fractions, including 4 having significant IC50/EC50 levels. F11 demonstrated the highest potential as T2D treatment, and the sequence identification provided the sequences SQQENELTSLIVESNNRFNNASNT. Natural bioactive peptides from easy to procure and cheap sources are promising molecules for therapeutic applications. Further in vivo and clinical testing are necessary to validate the current findings.

Hordeum vulgare (Barley grass) Scavenge Free Radical and Inhibits Formation of Advanced Glycation End Products Formation

Introduction: Advanced glycation end products (AGEs) formation is due to glycation of lipids, proteins, and nucleic acids. AGEs play a vital role in Diabetes Mellitus (DM) and cardiovascular complications and is enhanced by oxidative stress. Hordeum vulgare (Barley Grass) is a cereal plant of grass family poaceae and has been reported to exhibit antidiabetic and antioxidant characteristics and prevention of cardiovascular disease. Current experiment focused on the evaluation of antioxidant and anti-advanced glycation end products formation effect of Hordeum vulgare water extract. Methods: Free radical scavenging ability of Hordeum vulgare water extract, was evaluated using DPPH, nitric oxide, hydrogen peroxide, lipid peroxidation, FRAP and metal ion chelating. Total phenolic content of Hordeum vulgare was also analysed. In-vitro antiglycation activity was done using BSA-MGO, BSA-Glu. Phytochemical screening was performed to detect the presence of flavonoids, saponins, tannins, steroids and terpenoids. Results: The results showed Hordeum vulgare water extract ameliorated the formation of AGE and scavenge free radical from DPPH, Nitric oxide, hydrogen peroxide, Lipid peroxidation, FRAP and Metal ion chelating. Phytochemicals such as saponins, tannins, flavonoids, steroids and terpenoids were detected in Hordeum vulgare water extract. Conclusion: Hordeum vulgare water extract reveals antiglycation and free scavenging properties.

Digestive enzymes inhibition, antioxidant and antiglycation activities of phenolic compounds from jabuticaba (Plinia cauliflora) peel

In this study, jabuticaba peel purified phenolic extracts were studied regarding their potential inhibitory effects on digestive enzymes linked to diabetes mellitus (DM) and obesity, inhibitory activities towards glycation of bovine serum albumin (BSA), and antioxidant activities. The impact of in vitro gastrointestinal digestion (GID) on the stability of anthocyanins and bioactivities was also evaluated. The analyzed extracts exhibited significant inhibitory activities of α-glucosidase (IC50: 0.47–5.20 mg/mL), α-amylase (IC50: 0.45–1.88 mg/mL), and lipase (IC50: 13.52–111.51 mg/mL). The extracts also inhibited the glycation of BSA (IC50: 0.23–7.07 mg/mL) and showed relevant antioxidant activities. The correlation analysis indicated anthocyanins as one of the main contributing compounds to the bioactivities studied. Cyanidin-3-glucoside was the major anthocyanin identified in the extracts by HPLC analysis. After GID, there was a decrease in the total anthocyanin content (72.77% ± 1.67%) and, consequently, a reduction in the inhibitory activities of carbohydrate digestive enzymes and BSA glycation. This research provided scientific data about the functional properties of jabuticaba peel extracts, which may be a source of dietary compounds with hypoglycaemic, antiglycation, and antioxidant effects.

The Influence of Cationic Nitrosyl Iron Complex with Penicillamine Ligands on Model Membranes, Membrane-Bound Enzymes and Lipid Peroxidation.

This paper shows the biological effects of cationic binuclear tetranitrosyl iron complex with penicillamine ligands (TNIC-PA). Interaction with a model membrane was assessed using a fluorescent probes technique. Antioxidant activity was studied using a thiobarbituric acid reactive species assay (TBARS) and a chemiluminescence assay. The catalytic activity of monoamine oxidase (MAO) was determined by measuring liberation of ammonia. Antiglycation activity was determined fluometrically by thermal glycation of albumine by D-glucose. The higher values of Stern-Volmer constants (KSV) obtained for the pyrene located in hydrophobic regions (3.9 × 104 M-1) compared to KSV obtained for eosin Y located in the polar headgroup region (0.9 × 104 M-1) confirms that TNIC-PA molecules prefer to be located in the hydrophobic acyl chain region, close to the glycerol group of lipid molecules. TNIC-PA effectively inhibited the process of spontaneous lipid peroxidation, due to additive contributions from releasing NO and penicillamine ligand (IC50 = 21.4 µM) and quenched luminol chemiluminescence (IC50 = 3.6 μM). High activity of TNIC-PA in both tests allows us to assume a significant role of its radical-scavenging activity in the realization of antioxidant activity. It was shown that TNIC-PA (50-1000 μM) selectively inhibits the membrane-bound enzyme MAO-A, a major source of ROS in the heart. In addition, TNIC-PA is an effective inhibitor of non-enzymatic protein glycation. Thus, the evaluated biological effects of TNIC-PA open up the possibility of its practical application in chemotherapy for socially significant diseases, especially cardiovascular diseases.

Antiglycoxidative properties of amantadine – a systematic review and comprehensive in vitro study

An important drug used in the treatment of Parkinson’s disease is amantadine. We are the first to perform a comprehensive study based on various glycation and oxidation factors, determining the impact of amantadine on protein glycoxidation. Sugars (glucose, fructose, galactose) and aldehydes (glyoxal, methylglyoxal) were used as glycation agents, and chloramine T was used as an oxidant. Glycoxidation biomarkers in albumin treated with amantadine were generally not different from the control group (glycation/oxidation factors), indicating that the drug did not affect oxidation and glycation processes. Molecular docking analysis did not reveal strong binding sites of amantadine on the bovine serum albumin structure. Although amantadine poorly scavenged hydroxyl radical and hydrogen peroxide, it had significantly lower antioxidant and antiglycation effect than all protein oxidation and glycation inhibitors. In some cases, amantadine even demonstrated glycoxidant, proglycation, and prooxidant properties. In summary, amantadine exhibited weak antioxidant properties and a lack of antiglycation activity.

Inhibitory Effects of Parachlorella Beijerinckii Extracts on the Formation of Advanced Glycation End Products and Glycative Stress-Induced Inflammation in an In Vitro Skin Dermis-Like Model.

Advanced glycation end products (AGEs) are formed via a nonenzymatic glycosylation reaction called glycation. The formation and accumulation of AGEs increases in skin with age, contributing to the appearance of facial wrinkles and loss of skin elasticity. Therefore, inhibition of AGEs may delay skin aging. The microalgae Parachlorella beijerinckii has been used as a health food supplement for many years and contains carotenoids and vitamins that have antioxidant and anti-inflammatory effects. The aim of this study was to investigate whether Chlorella extract also has antiglycation activity. Antiglycation activity was measured using fluorescent AGEs, Nε-(carboxymethyl) lysine (CML), and Nε-(carboxymethyl) arginine (CMA) from glycated bovine serum albumin and type I collagen in vitro. A gel with a dermis-like structure consisting of collagen and a live fibroblast cell line was glycated with glyoxal. The content of fluorescent AGE, CML, and CMA, and the gel contraction activity were measured. In addition, to investigate the level of inflammation induced by the glycation of the collagen gel, the expression level of the receptor for AGEs and interleukin-8 were examined. Fat-solubleChlorella extract suppressed the formation of fluorescent AGEs, CML, and CMA in both models. These results indicated that Chlorella extract directly inhibited AGE formation. The collagen gel contracted over time during culturing, whereas contraction was inhibited in the glyoxal-treated collagen gel. Chlorella extract remarkably attenuated the glyoxal-induced gel contraction. Moreover, Chlorella extract substantially decreased the fluorescent AGEs, CML, and CMA in the collagen gels with glyoxal. Glyoxal exposure increased the expression levels of interleukin-8 and receptor for AGE proteins in collagen gels, while Chlorella extract inhibited this increase. This study showed that fat-solubleChlorella extract has a direct inhibitory effect on AGEs and decreases receptor expression for AGE-mediated inflammation by reducing AGEs. Chlorella may delay skin aging by inhibiting the formation and accumulation of AGEs.

Structure analysis and tyrosinase, melanogenesis, α-glucosidase, and nonenzymatic glycation inhibitory activities of polymeric proanthocyanidins from the pulp of Crataegus pinnatifida Bge.

Crataegus pinnatifida Bge. is a worthwhile industrial crop for its extensive application in Chinese herbal pharmaceuticals, food, and other industries. In this study, proanthocyanidins were extracted from the pulp of Crataegus pinnatifida Bge., and the structure, antityrosinase, antimelanogenesis, anti-α-glucosidase, and anti-glycation activities of these compounds were systematically elucidated. The combined utilization of high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS), matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), and nuclear magnetic resonance (NMR) demonstrated that the proanthocyanidins were B-type procyanidin polymers consisting of epicatechin . These polymers were efficient, reversible, and competitive inhibitors of both tyrosinase and α-glucosidase with IC 50 values of 0.10 ± 0.01 mg/mL (for monophenolase), 0.16 ± 0.02 mg/mL (for diphenolase), and 0.50 ± 0.02 µg/mL, respectively. Moreover, the process of nonenzymatic glycation was also delayed by proanthocyanidins. Further cell assays suggested that these polymers strongly inhibited intracellular tyrosinase activity and melanogenesis and induced apoptosis in mouse melanoma cells. The results of circular dichroism (CD), molecular docking , and molecular dynamics (MD) consistently revealed that the inhibition of procyanidins on the two enzymes was primarily driven by hydrogen bonding and hydrophobic interactions, and the binding of epicatechin caused structural stretching and conformational modification of tyrosinase. Consequently, this study confirms novel tyrosinase, melanogenesis, α-glucosidase, and nonenzymatic glycation inhibitors, which might offer scientific evidence for potential applications in the cosmetics and pharmaceutical industries. • Proanthocyanidins can be produced industrially for a yield of 11.08%. • Various biological activities of proanthocyanidins enabled their wide applications. • Hydrogen bond and hydrophobic interaction loosened tyrosinase secondary structures. • Proanthocyanidins can reduce melanogenesis by down-regulating tyrosinase proteins.

Discovering biological efficacy of new thiadiazole as effective inhibitors of urease, glycation, and (DPPH) scavengers: Biochemical and in silico study

Thiadiazole is a potential class of α-glucosidase, β-glucuronidase, and anti-leishmanial inhibitors. Our aim was to develop thiadiazole based dual inhibitors for urease glycation inhibition and (DDPH) scavenging activity. Pyridine-based-thiadiazole analogs (1–18) were synthesized and characterized through 1H NMR, 13C NMR, EI-HRMS. All synthesized compounds were new and showed good inhibition ranging between IC50 value (0.70 ± 0.010 to 21.10 ± 0.90 μM) when compared with standard thiourea (21.40 ± 0.21 μM). Among the series, analog 13 having IC50 value (0.70 ± 0.010) showed the most potent inhibition. All synthesized compounds screened for their antioxidant and antiglycation inhibitory effect, and they showed good inhibition for both. The binding interactions with urease enzyme with active inhibitors studied via molecular docking studies. The compound 13 showed potent urease, antiglycation and (DPPH) scavenging activity and showed its character as dual inhibitor.

Synthesis of Arylidenehydrazinyl-4-methoxyphenylthiazole Derivatives: Docking Studies, Probing Type II Diabetes Complication Management Agents.

Thiazole has been a key scaffold in antidiabetic drugs. In quest of new and more effective drugs a simple, efficient, high yielding (67-79 %) and convenient synthesis of arylidenehydrazinyl-4-methoxyphenyl)thiazoles is accomplished over two steps. The synthesis involved the condensation of aryl substituted thiosemicarbazones and 2-bromo-4-methoxyacetophenone in absolute ethanol. The structures of the resulting thiazoles are in accord with their UV/VIS, FT-IR, 1 H-, 13 C-NMR and HRMS data. All compounds were evaluated for alpha(α)-amylase inhibition potential, antiglycation, antioxidant abilities and biocompatibility. The compounds library identified 2-(2-(3,4-dichlorobenzylidene)hydrazinyl)-4-(4-methoxyphenyl)thiazole as a lead molecule against α-amylase inhibition with an IC50 of 5.75±0.02 μM. α-Amylase inhibition is also supported by molecular docking studies against α-amylase. All the obtained thiazoles also showed promising antiglycation activity with 4-(4-methoxyphenyl)-2-{2-[2-(trifluoromethyl)benzylidene]hydrazinyl}thiazole exhibiting the best inhibition (IC50 = 0.383±0.001 mg/mL) compared to control. The tested compounds are also biocompatible at the concentration used i. e., 10 μM.

Lignin, an active component in the corn silk water extract, inhibits glycation

The formation of advanced glycation end products is associated with aging and diabetic complications such as neuropathy, retinopathy, and nephropathy. Thus, the suppression of AGEs formation could prevent and/or treat their related disorders. Corn silk is used as a traditional medicine for the prevention of diabetic complications and treatment of edema in Japan and China. Previous studies revealed the anti-glycation activity of flavonoids in the methanolic extract of corn silk. The anti-glycation activity of the corn silk water extract was higher than that of the methanolic extract; however, the active components of the water extract remained unidentified. The purpose of this study is to make clear the components showing anti-glycation activity in the corn silk water extract and elucidated their structural characteristics. The evaluation of anti-glycation activity was carried out by enzyme-linked immunosorbent assay to detect glycated bovine serum albumin. Remarkable anti-glycation activity was observed in the > 3 kDa fraction. Reversed-phase HPLC analysis of this fraction showed broad peaks characteristic of high-molecular-weight polyphenols. Decomposition reactions did not provide evidence of condensed or acid-hydrolyzable tannins. Therefore, polyphenols contained in the corn silk water extract were considered to be lignin-carbohydrate complex. The 1H- and 13C-nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectroscopy spectra of the > 3 kDa fraction were in agreement with the values reported for lignin. Consequently, we concluded that lignin-carbohydrate complex is one of the active components against glycation in the corn silk water extract.

In vitro α-amylase and hemoglobin glycation inhibitory potential of Nigella sativa essential oil, and molecular docking studies of its principal components.

Nigella sativa is plant that is endowed with various pharmacological activities including antioxidant, anticancer, anti-inflammatory, antibacterial, antidiabetic, and immunostimulant. This study aims to investigate the antidiabetic activity of the N. sativa essential oil on two key enzymes the α-amylase and hemoglobin glycation. After the extraction procedure, the N. sativa essential oil, were subject to qualitative and semi-quantitative analysis using GC/MS, for the identification of the different bioactive compounds. This was followed by an evaluation of the in vitro inhibition capacity of the α-amylase and the hemoglobin glycation. Finally, a molecular docking study was conducted to determine the bioactive compounds responsible for the antidiabetic activity. The extracted essential oil showed the presence of different bioactive compounds including α-phellandrene (29.6%), β-cymene (23.8%), 4-caranol (9.7%), thymol (7%). The N. sativa essential oil was found to be endowed with an antiradical scavenging activity with an IC50 of (7.81 ± 0.08mg/ml), and to have a ferric reducing activity with an IC50 value of (7.53 ± 0.11mg/ml). The IC50 value for the α-amylase inhibitory activity was 0.809mg/ml, indicating an inhibitory impact of the enzyme. The IC50 value for the N. sativa essential oil's hemoglobin antiglycation activity was 0.093mg/ml. For most predominating phytochemicals present in the N. sativa essential oil, molecular docking studies against human pancreatic α-amylase and human hemoglobin enzymes revealed that these compounds can serve as lead molecules to develop new antidiabetic compounds.

Guanidine Derivatives of Quinazoline-2,4(1H,3H)-Dione as NHE-1 Inhibitors and Anti-Inflammatory Agents.

Quinazolines are a rich source of bioactive compounds. Previously, we showed NHE-1 inhibitory, anti-inflammatory, antiplatelet, intraocular pressure lowering, and antiglycating activity for a series of quinazoline-2,4(1H,3H)-diones and quinazoline-4(3H)-one guanidine derivatives. In the present work, novel ,-bis-substituted quinazoline-2,4(1H,3H)-dione derivatives bearing two guanidine moieties were synthesized and pharmacologically profiled. The most potent NHE-1 inhibitor 3a also possesses antiplatelet and intraocular-pressure-reducing activity. Compound 4a inhibits NO synthesis and IL-6 secretion in murine macrophages without immunotoxicity and alleviates neutrophil infiltration, edema, and tissue lesions in a model of LPS-induced acute lung injury. Hence, we considered quinazoline derivative 4a as a potential agent for suppression of cytokine-mediated inflammatory response and acute lung injury.

Chemometric discrimination of Hylocereus undulatus from different geographical origins via their metabolic profiling and antidiabetic activity

Hylocereus spp. known as dragon fruit is an exotic fruit that belongs to the Cactaceae family. LC-QTOF-MS and multivariate statistical tools were established to analyze differences in the composition of dragon fruit peel and pulp from Egypt, Germany, Philippines, and China. The α-glucosidase inhibitory effects of different extracts were carried out along with the anti-glycation end products (AGE) using BSA-fructose, BSA-methylglyoxal, and arginine-methylglyoxal assays. In addition, the total antioxidant capacity was investigated as a complementary mechanism to AGE formation. Principal component analysis revealed that dragon fruits from China and Egypt were the most distinct among all samples due to betalains content. Orthogonal projection to latent structures-discriminant analysis identified 16 compounds highly correlated to the antiglycation activity such as betanin, γ-aminobutyric acid, neobetanin, and portulacaxanthin II. Pulp extracts were more active than peels as inhibitors of α-glucosidase. While peels were more active as AGE formation inhibitors and as antioxidants.

Inhibitory Effects of Myriocin on Non-Enzymatic Glycation of Bovine Serum Albumin.

Advanced glycation end products (AGEs) are the compounds produced by non-enzymatic glycation of proteins, which are involved in diabetic-related complications. To investigate the potential anti-glycation activity of Myriocin (Myr), a fungal metabolite of Cordyceps, the effect of Myr on the formation of AGEs resulted from the glycation of bovine serum albumin (BSA) and the interaction between Myr and BSA were studied by multiple spectroscopic techniques and computational simulations. We found that Myr inhibited the formation of AGEs at the end stage of glycation reaction and exhibited strong anti-fibrillation activity. Spectroscopic analysis revealed that Myr quenched the fluorescence of BSA in a static process, with the possible formation of a complex (approximate molar ratio of 1:1). The binding between BSA and Myr mainly depended on van der Waals interaction, hydrophobic interactions and hydrogen bond. The synchronous fluorescence and UV-visible (UV-vis) spectra results indicated that the conformation of BSA altered in the presence of Myr. The fluorescent probe displacement experiments and molecular docking suggested that Myr primarily bound to binding site 1 (subdomain IIA) of BSA. These findings demonstrate that Myr is a potential anti-glycation agent and provide a theoretical basis for the further functional research of Myr in the prevention and treatment of AGEs-related diseases.

Design, Synthesis, Crystal Structure, In Vitro and In Silico Evaluation of New N'-Benzylidene-4-tert-butylbenzohydrazide Derivatives as Potent Urease Inhibitors.

Background: Hydrazides play a vital role in making biologically active compounds in various fields of chemistry. These determine antioxidant, antidepressant, antimalarial, anti-inflammatory, antiglycating, and antimicrobial activity. In the present study, twenty-three new N′ benzylidene-4-(tert-butyl)benzohydrazide derivatives (4–26) were synthesized by the condensation of aromatic aldehydes and commercially available 4-(tert-butyl)benzoic acid. All the target compounds were successfully synthesized from good to excellent yield; all synthesized derivatives were characterized via spectroscopic techniques such as HREI-MS and 1H-NMR. Synthesized compounds were evaluated for in vitro urease inhibition. All synthesized derivatives demonstrated good inhibitory activities in the range of IC50 = 13.33 ± 0.58–251.74 ± 6.82 µM as compared with standard thiourea having IC50 = 21.14 ± 0.425 µM. Two compounds, 6 and 25, were found to be more active than standard. SAR revealed that electron donating groups in phenyl ring have more influence on enzyme inhibition. However, to gain insight into the participation of different substituents in synthesized derivatives on the binding interactions with urease enzyme, in silico (computer simulation) molecular modeling analysis was carried out.