Antiglycation Agents Research Articles

Synthesis, biological evaluation, molecular docking and structure-activity relationship studies of halogenated quinone and naphthoquinone derivatives

Protein glycation, oxidative stress and acetyl cholinesterase enzyme (AChE) are closely implicated in the pathogenesis of diabetic complications and Alzheimer's disease. In this study, we synthesized a series of previously unexplored molecular analogues of halogenated quinone and naphthoquinone to investigate their therapeutic potency against protein glycation, free radical production and acetyl cholinesterase enzyme.The study on protein glycation resulted in the identification of two novel antiglycation agents such as 2,3-dichloronaphthalene-1,4-bistriflate (3) and 2,3-dibromonaphthalene-1,4-bis (trifluoromethanesulfonate) (6) with IC50 values less than 16 micromolar range. Moreover, 2,3-dichloro-1,4- naphthoquinone (DCNQ) (1), 2,3-dibromonaphthoquinone (4), 2,3-dibromonaphthalene-1,4-diol (5) and 2,3,5,6-tetrachlorobenzene-1,4-bis(trifluoromethane- sulfonate) (8) exhibited potent antiglycation activity with IC50 values of 54 ± 1.02, 43 ± 0.5, 65 ± 1.00 and 60 ± 1.25 μM, respectively as compared to the standard inhibitor rutin with an IC50 value of 98 ± 1.50 μM. The structure-activity relationship (SAR) demonstrated that the presence of bis-(trifluoromethanesulfonate) as substituents alongwith halogens moieties appreciably influenced inhibitory potential and enhanced the antiglycation potential significantly. On free radical DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging assay, 2,3,5,6-tetrachlorobenzene-1,4-bis(trifluoromethane- sulfonate) (8), showed significant antioxidant activity with IC50 values 52 ± 1.50 μM. On acetyl cholinesterase inhibition assay, compound 8 and 2,3-dichloronaphthalene-1,4-bistriflate 3, exhibited considerable inhibition with IC50 values of 98 ± 1.00 μM and 124 ± 1.50 μM, respectively. The SAR studies against AChE revealed that the presence of chlorine and trifluoromethanesulfonate both combined together in a compound enhanced its inhibitory activity several folds. In support of experimental observations, molecular docking studies with the active site of acetyl cholinesterase also confirmed the stronger inhibition of compounds 3, and 8 compared to others derivatives. These inhibitors demonstrated hydrogen bonding with Tyr124 and π-π stacking with Tyr341 of the active site residues. In this study, galantamine, rutin and propyll gallate were used as standard inhibitors, respectively.

Investigation and isolation of peptide based antiglycating agents from various sources

Abstract Background In this work, peptide based antiglycation agents from various sources against the advanced glycation endproducts (AGE) formation was investigated. Materials and methods As a source of peptides with deglycating activity, Glycine max, Hordeum vulgare, Triticum aestivum, Avena sativa, Prunus dulcis ve Juglans regia were used. The metal chelating activity and antioxidant activity were determined by Cu(II) chelating activity and CUPRAC (Cupric Reducing Antioxidant Capacity) methods. Antidiabetic activity was evaluated through BSA-glucose model. Results Most of the extracts obtained have inhibitory activity against AGE formation. Among all plant peptide isolates soybean was found to be most efficient by means of antiglycating (IC50 1.33 μg/mL), antioxidant (28.2 ± 1.4 μmol AAE/mg) and metal chelation activity (55%). Conclusion As a result, this study can provide preliminary data to literature to support researches those focused on peptide based glycation inhibitors and discovery of potent AGE inhibitory peptides.

Using Neuroscience, Contemporary methods and Traditional Wisdom in Building Well-being in Long Term Unemployed Youth

Advanced glycation end-products (AGEs) from non-enzymatic glycation are implicated in several degenerative diseases, including being a crucial contributor in secondary complications of diabetes. This has garnered significant scientific interest in inhibiting agents of AGEs to prevent and remediate disorders arising due to glycation. In the current study, inhibitory effects on AGEs formation were investigated using bio-enzymatically synthesized nanoformulations of gold (AuNPs) and silver (AgNPs) by physiologically important enzyme, β galactosidase. Human serum albumin, most abundant protein in human blood plasma, was glycated by incubating with glucose leading to AGEs formation. The AGEs formation was significantly minimized with both AuNPs and AgNPs, as confirmed by various biophysical and biochemical techniques. Circular dichroism and Fourier transform infrared spectroscopy further affirmed antiglycation potential of AuNPs and AgNPs. The results were corroborated with thiol group, free lysine and carbonyl content estimation for native, glycated and nanoparticles (NPs) treated samples. Confocal microscopic imaging was performed to exhibit glycation inhibiting potential of the NPs. The inhibition of AGEs was observed to be slightly stronger in case of AgNPs than AuNPs with both exhibiting promising results as potential anti-glycating agents. The study sheds light on potential of non-toxic NPs being utilized as controlling agents against hyperglycemic conditions and diabetes management.

Suppression in advanced glycation adducts of human serum albumin by bio-enzymatically synthesized gold and silver nanoformulations: A potential tool to counteract hyperglycemic condition

Advanced glycation end-products (AGEs) from non-enzymatic glycation are implicated in several degenerative diseases, including being a crucial contributor in secondary complications of diabetes. This has garnered significant scientific interest in inhibiting agents of AGEs to prevent and remediate disorders arising due to glycation. In the current study, inhibitory effects on AGEs formation were investigated using bio-enzymatically synthesized nanoformulations of gold (AuNPs) and silver (AgNPs) by physiologically important enzyme, β galactosidase. Human serum albumin, most abundant protein in human blood plasma, was glycated by incubating with glucose leading to AGEs formation. The AGEs formation was significantly minimized with both AuNPs and AgNPs, as confirmed by various biophysical and biochemical techniques. Circular dichroism and Fourier transform infrared spectroscopy further affirmed antiglycation potential of AuNPs and AgNPs. The results were corroborated with thiol group, free lysine and carbonyl content estimation for native, glycated and nanoparticles (NPs) treated samples. Confocal microscopic imaging was performed to exhibit glycation inhibiting potential of the NPs. The inhibition of AGEs was observed to be slightly stronger in case of AgNPs than AuNPs with both exhibiting promising results as potential anti-glycating agents. The study sheds light on potential of non-toxic NPs being utilized as controlling agents against hyperglycemic conditions and diabetes management.

Characterization of collagen and its hydrolysate from yellowfin tuna Thunnus albacares skin and their potencies as antioxidant and antiglycation agents

Collagen is one of the biopolymer proteins that may be useful for food and non-food purposes. Recently, even for collagen, it is becoming necessary to meet the requirements of “halal” for Muslim societies, and thus fish-derived collagen is regarded as ideal. Utilization of tuna skin as an alternative source of collagen would increase its market value, and there is an abundant catch in south west Asian regions. Thus, the purpose of this study was to prepare and characterize collagen from the skin of yellowfin tuna using a plant-derived protease, papain. The obtained collagen was further hydrolyzed with Alcalase, and the peptides fractionated by gel filtration chromatography were subjected to antioxidant and antiglycation activity assays. The results showed high activities of hydrolysate in these parameters.

Pectin oligosaccharides from hawthorn (Crataegus pinnatifida Bunge. Var. major): Molecular characterization and potential antiglycation activities

The crude polysaccharide was extracted from hawthorn (Crataegus pinnatifida Bunge. Var. major) and a salt-eluted polysaccharide (SPS-2) was fractionated by DEAE cellulose-52 chromatography. Monosaccharide composition and Fourier-transform infrared (FT-IR) analysis indicated that the SPS-2 contained 72.3% galacturonic acid and may be pectin. The results of antiglycation activity in vitro showed that the medium molecular weight pectin oligosaccharide (MM-POS) had the highest antiglycation activity among SPS-2 degradation products. Moreover, the MM-POS obtained by enzymatic degradation had stronger antiglycation activity than that by ultrasonic assisted enzymatic degradation. Composition analysis of MM-POS obtained from ultrasound-assisted enzymatic degradation showed that polygalacturonans content decreased from 85.1% to 61.9% but the arabinan and rhamnogalacturonans increased from 10.6% to 22.7% and from 3.5% to 13.2%, respectively, compared to the MM-POS obtained from enzymatic degradation. This study will provide a theoretical basis for the application of POSs in the food field, especially the exploitation of antiglycation agents.

Propolis nanoparticles prevent structural changes in human hemoglobin during glycation and fructation

Nowadays diabetes, as a metabolic disorder, is increasing at an alarming rate. Glycation and production of advanced glycation end products (AGEs) is the most important factor involved in diabetic complications. Due to the side effects of synthetic drugs, the demand for natural anti-diabetic herbal medicines has increased. Propolis is a natural and resinous material, which iscollected by honeybees. Due to the impact of nanotechnology in medicine and the advantageous role of nanoparticles in treatment, nano-propolis particles (PNP) were prepared. The anti-glycation effect of PNP at various concentrations was investigated on human hemoglobin (Hb) glycation and fructation and compared with aspirin as a common anti-glycation agent using glycation specific AGE fluorescence, AGE-specific absorbance and circular dichroism (CD) methods. Fluorescence spectroscopy results showed that PNP inhibited the formation of AGEs in Hb glycation and fructation by glucose and fructose, respectively. CD results revealed that PNP caused an increase in Hb beta-sheet content while decreasing the alpha helical content. Additionally, the results of UV-Vis spectroscopy and fluorescence emission of heme degradation products revealed the protective effect of PNP on heme during glycation and fructation of human Hb. It is notable that the synergistic effects of combined propolis nanoparticles and aspirin is more than either of them alone. However, having said that, PNP as a natural product has a potential to be an effective drug in the treatment of diabetes.

Potential Antiglycation and Hypoglycaemic Effects of Toona ciliata M. Roem. and Schkuhria pinnata Lam. Thell. Crude Extracts in Differentiated C2C12 Cells.

Medicinal plants have been identified as a feasible avenue for the development of new potent antidiabetic agents. The phytoconstituent compositions of different Toona ciliata and Schkuhria pinnata extracts were determined and quantified using standard chemical methods after exhaustive extraction. Thereafter, their antioxidant and antiglycation potentials were spectrophotometrically determined. The cytotoxicity profiles of the extracts on C2C12 cells were determined using the MTT assay. Toona ciliata methanol extract resulted in the highest percentage yield (20.83%) and high total phenols and flavonoids content in the methanol and acetone extracts compared to S. pinnata extracts. The acetone extract of T. ciliata showed good activity in the DPPH scavenging and FRAP assays with EC50 values of 1.90 mg/ml and 5.26 mg/ml, respectively. Arbutin's antiglycation ability was outperformed by treatments with the methanol, acetone, and hexane extract of T. ciliata which resulted in 2.49%, 2.79%, and 2.56% glycation, respectively. The hexane extract of T. ciliata was less toxic to C2C12 cells as compared to the other extracts with CC50 value of 402.16 μg/ml. Only the hexane extract of S. pinnata resulted in glucose utilisation of 28.56% which was higher than that of insulin (26.06%) after 6 hours and is therefore considered as the most potent extract with hypoglycaemic potential in this study. Studies are ongoing aimed at identifying drug candidates in this extract that may be employed in the development of hypoglycaemic, antioxidant, and antiglycation agents.

Liquid state fermentation vinegar enriched with catechin as an antiglycative food product.

Catechin, a natural antiglycative agent, was incorporated into fermented vinegar, and has high potential to lower the risk of diabetes. In this study, vinegar containing 5% catechin as a substrate for acetous fermentation significantly inhibited the formation of total fluorescent advanced glycation end-products (AGEs), as well as Nε-(carboxymethyl)lysine (CML)/Nε-(carboxyethyl)lysine (CEL), especially when added during acetic fermentation. Further study proved that catechin could not only significantly suppress the increase of blood glucose levels, but also inhibit α-amylase, α-glucosidase and β-glucosidase strongly with IC50 values of 0.533 mg mL-1, 0.307 mg mL-1 and 0.413 mg mL-1, respectively. Moreover, 32 volatile compounds were finally identified by headspace solid phase microextraction gas chromatography-mass spectrometry (HSPM-GC-MS) and electronic nose. The flavor of the catechin-vinegars, which possess relatively high ester and low acid contents, was superior to that of traditional vinegar. Therefore, it was helpful to use catechin as a functional food ingredient in vinegar to prevent AGE-associated diseases and alleviate postprandial hyperglycemia, through limiting the digestion of starch and inhibiting the uptake of glucose. Meanwhile, the pleasant flavor and safety of catechin-vinegar were better than traditional vinegar, which represents prominent value to attract consumers.

Pectin oligosaccharides from hawthorn (Crataegus pinnatifida Bunge. Var. major) inhibit the formation of advanced glycation end products in infant formula milk powder.

Pectin oligosaccharides (POSs) can not only be used as prebiotics to promote the growth of beneficial bacteria in the intestine but also can be used as natural food-borne antiglycation agents to inhibit the formation of advanced glycation end products (AGEs) in vitro, which is related to their structure, including molecular weight and galacturonic acid content. In this study, haw polysaccharides (HPSs) were isolated and purified, and POSs with high antiglycation activity in vitro were prepared. On this basis, the inhibitory effect of POSs on the formation of AGEs in infant formula milk powder was investigated. The results showed that no obvious inhibitory effect of POSs was found on the formation of AGEs in infant formula milk powder under accelerated storage at 25 °C and 45 °C. But, POSs showed a strong inhibitory effect on the formation of furosine, Nε-carboxymethyllysine (CML), Nε-carboxyethyllysine (CEL) and the total AGEs in infant formula milk powder under accelerated storage at 65 °C. In addition, POSs also had a strong inhibitory effect on the formation of lipid oxidation products but did not affect the formation of protein degradation products. Simultaneously, the cytotoxicity experiments using human umbilical vein endothelial cells showed that the infant formula milk powder supplemented with POSs had the lowest cytotoxicity compared to the blank control (BC) and GOS/FOS supplementation milk powder under accelerated storage at 65 °C, which may be related to the inhibitory effect of POSs on the formation of AGEs in infant formula milk powder. Furthermore, the in vitro fermentation experiments showed that the antiglycation process did not affect the prebiotic activity of POSs in infant formula milk powder.

Identification of Pinocembrin as an Anti-Glycation Agent and α-Glucosidase Inhibitor from Fingerroot (Boesenbergia rotunda): The Tentative Structure⁻Activity Relationship towards MG-Trapping Activity.

Diabetes mellitus (DM) is a disease that is caused by a malfunction of carbohydrate metabolism, which plays an important role in the development of long-term diabetic complications. The excess glucose can be transformed to methylglyoxal (MG), a potential precursor of glycation. Glycation is a spontaneous non-enzymatic reaction that initially yields advanced glycation end-products (AGEs), which ultimately triggers several severe complications. Therefore, the inhibition of AGEs formation is the imperative approach for alleviating diabetic complications. The aim of this research was to investigate the glycation and α-glucosidase inhibitory abilities of compounds isolated from fingerroot. The dichloromethane extract afforded three flavanones, two chalcones, two dihydrochalcones, and one kavalactone. Most of the isolated compounds showed higher inhibition effect against AGEs formation than aminoguanidine (AG). Subsequent evaluation in MG-trapping assay indicated that their trapping potency was relatively comparable to AG. Their structure-activity relationships (SAR) of MG-trapping activity were investigated using the comparison of the structures of flavonoids. In addition, pinocembrin displayed moderate α-glucosidase inhibition against both maltase and sucrose, with IC50 values of 0.35 ± 0.021 and 0.39 ± 0.020 mM, respectively.

Inhibitory effect of silibinin on Amadori-albumin in diabetes mellitus: A multi-spectroscopic and biochemical approach.

Due to increased understanding of the damaging effects of glycation process, it is highly desirable to manage this process effectively either by prevention or by managing the consequences of glycation preferentially at early stage. The use of potential naturally occurring compounds as anti-glycating agents may provide an effective approach to control the development and progression of diabetic associated complications. In the present study, human serum albumin (albumin) was co-incubated with glucose and different concentrations of silibinin. Silibinin was demonstrated to possess anti-glycation activity. We found that silibinin inhibits glucoseinduced glycation at an early stage. We analyzed the effect of silibinin on albumin structure and its biochemical properties at early stage of glycation through various biophysical and biochemical techniques. Nitro blue tertazolium assay results showed that fructosamine formation was reduced in the presence of silibinin. UV-visible spectra results showed decrease in the absorbance with increasing concentrations of silibinin towards native albumin absorbance. Fluorescence results showed that the intensity was increased with increasing the silibinin concentrations as compared to Amadori-albumin. In addition, Far-UV CD spectra demonstrated some restoration of α-helicity when albumin was incubated with glucose in the presence of silibinin. Moreover, silibinin caused significant reduction in carbonyl contents with concomitant increase in free thiol, lysine and arginine residues. The anti-glycation activity of silibinin was concentration-dependent. From all the observations, we can conclude that silibinin might be acting as an obstacle in the binding of glucose with albumin and thus preventing the glycation induced changes in albumin. Silibinin may be effective in delaying glycation mediated pathologies in diabetic individuals.

Microencapsulation of grape skin phenolics for pH controlled release of antiglycation agents

Grape skin (GS) phenolics can prevent structural damage of proteins due to reducing sugars or dicarbonyl compounds, which is the leading cause of hyperglycaemia damage and is involved in inflammatory diseases. In this study, alginate hydrogel was used to encapsulate GS phenolics as a pH dependent releasing system. Microbeads were obtained by a vibrating nozzle method using calcium chloride as hardening agent. Encapsulation efficiency for total phenolics was 68%. At pH 1.4, the alginate microbeads remained intact and only 13% of total phenolic compounds of the microbeads was released. The percent release depended on the compound: procyanidin B1 release was 74%, catechin and epicatechin release was ~ 50%, while anthocyanin and flavonol release was less than 11%. At pH 7.4, the microbeads were dissolved and formed a viscous solution that showed ability to protect bovine serum albumin from glycation induced by both fructose and methylglyoxal. The antiglycation activity was 246 mmol catechin equivalents (CE)/kg of dry microbeads in the fructose model system and 78 mmol CE/kg of dry microbeads in the methylglyoxal model system. These values corresponded to 68% and 62% of the expected activity, probably due to interaction between phenolics and the alginate carrier. Despite the recovery of antiglycation activity was incomplete, results of this study confirmed the efficiency of alginate to act as a pH controlled released system for GS phenolics. This functionalized polymer could be applied in the prevention of advanced-glycation-endproducts related diseases.

Silver Nanoparticles Synthesized Using Eysenhardtia polystachya and Assessment of the Inhibition of Glycation in Multiple Stages In Vitro and in the Zebrafish Model

The aim was to investigate the inhibitory activities on AGE formation by testing silver nanoparticles fabricated using a methanol extract of Eysenhardtia polystachya (EP–AgNPs) and characterized using various physicochemical techniques. The in vitro glucose-albumin assay was used, and cell viability was carried out in RAW264.7 cells. For In vivo testing, we induced diabetes in adult zebrafish with by providing a high blood glucose concentration. EP–AgNPs showed an absorption peak at 413 nm in the UV–Vis spectrum, indicating surface plasmon resonance of the nanoparticles. TEM indicated that most of the particles were spherical, with a diameter of 10–12 nm, a polydispersity index of 0.197, and a zeta potential of − 32.25 mV, suggesting high stability of the nanoparticles. The biocompatible nature of the EP–AgNPs was demonstrated in RAW264.7 cells. EP–AgNPs markedly reduced the formation of AGEs, Amadorin-product/fructosamine, Ne-(carboxymethyl)-lysine, amyloid cross β-structure, and protein carbonyl content in BSA-glucose system and increased total thiol-group after 4 weeks in hyperglycemic zebrafish, EP–AgNPs provided a protective effect against glycation. Data suggest that the inhibitory activity of EP–AgNPs on formation of AGEs is developed through a multiple-stage mechanism of glycation. EP–AgNPs could therefore be an antiglycation agent for prevention diabetic complications.

Anthranilic Acid Derivatives: Novel Inhibitors of Protein Glycation and the Associated Oxidative Stress in the Hepatocytes.

Anthranilic acid derivatives are important pharmacophores in drug discovery. Several of them are currently being used, such as mefenamic acid and meclofenamates, possess analgesic, anti-inflammatory and antipyretic activities. Some anthranilic acid-based scaffolds have also been reported for the management of metabolic disorders. The aim of the current study was to investigate the antiglycation potential of 2-anilino benzoic acid derivatives against (N-phenylanthranilic acid) fructose- human serum albumin (HSA) glycation. The study also analyzed the effects of newly identified antiglycation inhibitors on AGEs-mediated intracellular reactive oxygen species production, and associated impaired proliferation of the hepatocytes. The present study focuses on the antiglycation activity of 2- anilinobenzoic acid derivatives 1-18 in in-vitro human serum albumin (HSA)- fructose model. These derivatives were also identified as non-toxic to 3T3 mouse fibroblast cell-line using metabolic assay. The effect of the most promising derivative 1, 2- (2, 4- dinitroanilino)benzoic acid, was studied in a dose dependent manner, co-incubated with fructose-derived AGEs (0- 200 μg/mL), on rat hepatocytes proliferation and associated intracellular generation of ROS via MTT assay and DCFH-DA technique, respectively. We found that derivative 1 ameliorates the elevated intracellular oxidative stress and associated diminished proliferation of the hepatocytes in response to AGEs. In conclusion, we identify novel 2- anilino benzoic acid derivatives as antiglycation agents through in-vitro and cellular-based models.

Impact of wedelolactone in the anti‐glycation and anti‐diabetic activity in experimental diabetic animals

The glycation reaction is the addition of free carbonyl group of reducing sugar to the free amino groups of proteins, lipoproteins and nucleic acids which results in the formation of an Amadori product which may ultimately lead to the generation of advanced glycation products (AGEs). The impact of AGEs on proteins consequently generates free radicals, "a key player" for the pathogenesis of diabetes mellitus. Gel electrophoresis was carried out to see the visual changes taking place as a result of the glycation reaction. In this study, the anti-glycation and anti-diabetic effect of wedelolactone (WED) was seen both in vitro and in vivo. WED reverted various biochemical markers in streptozotocin-induced diabetic rats along-with the improvements in the oxidative stress markers. It also decreased the levels of the glycated serum protein and fasting blood glucose. Broadly, WED not only inhibited glycation in vitro but also proved to be an effective in vivo anti-glycating agent. © 2018 IUBMB Life, 70(6):547-552, 2018.

Isoferulic acid attenuates methylglyoxal-induced apoptosis in INS-1 rat pancreatic β-cell through mitochondrial survival pathways and increasing glyoxalase-1 activity

Methylglyoxal (MG) is a reactive precursor to advanced glycation end-products (AGEs), which exert deleterious effects on cells and tissues. MG also causes pancreatic β-cell dysfunction and apoptosis. Isoferulic acid (IFA), a naturally occurring cinnamic acid derivative, is considered to be an antiglycating agent. However, the effect of IFA on MG-induced pancreatic β-cell dysfunction remains unknown. The objective of this study was to determine the protective effect of IFA against MG-induced mitochrondrial dysfunction and apoptosis in INS-1 pancreatic β-cells. The results showed that pretreatment of INS-1 cells with 100 μM IFA for 48 h prevented MG-induced decrease in cell viability and impairment of glucose-stimulated insulin secretion (GSIS). In addition, 100 μM IFA pretreatment also decreased MG-induced generation of reactive oxygen species (ROS) and upregulation of mitochondrial uncoupling protein 2 (Ucp2) mRNA expression. Furthermore, IFA pretreatment reduced MG-induced increase in caspase-3 activity, suggesting a reduction of apoptotic cell death. IFA (50–100 μM) itself markedly increased the activity of glyoxalase 1 (GLO1), a major enzyme for the detoxification of MG. The results showed that 100 μM IFA protected MG-induced loss of GLO1 activity in INS-1 cells. These findings suggest that IFA pretreatment attentuates MG-induced dysfunction and apoptosis in INS-1 pancreatic β-cells through mitochondrial survival pathway and increasing GLO1 activity.

Antiglycation and antioxidant activities of mogroside extract from Siraitia grosvenorii (Swingle) fruits.

Siraitia grosvenorii (Swingle) is one kind of medical and edible plants with various health-promoting properties. Recently, its hypoglycemic and antidiabetic activities have been reported, but the underlying mechanism remains to be explored. The current study was aimed to investigate the antioxidant and antiglycation activities of mogroside extract (MGE) from Siraitia grosvenorii (Swingle). The results showed that compared to glycated BSA, MGE at middle (125μg/mL) and high dose (500μg/mL) significantly inhibited BSA glycation evidenced by decreased fluorescent AGEs formation, protein carbonyls and Nε-(carboxymethyl) lysine (CML) level at 500μg/mL by 58.5, 26.7 and 71.2%, respectively. Additionally, the antiglycative activity of MGE (500μg/mL) was comparable to aminoguanidine (AG) at the equal concentration. However, the inhibitory effect of MGE on glycation-induced increase of fructosamine level and decrease of thiol level was not remarkable. MGE was a potent peroxide radicals scavenger (851.8μmol TE/g), moderate DPPH and ABTS radicals scavenger with IC50 1118.1 and 1473.2μg/mL, respectively, corresponding to positive controls ascorbic acid of IC50 9.6μg/mL, and trolox of IC50 47.9μg/mL, respectively, and mild reducing power. These findings suggest that MGE may serve as a new promising antiglycative agent against diabetic complications by inhibiting protein glycation and glycoxidation.

Inhibiting Effect of Zinc Oxide Nanoparticles on Advanced Glycation Products and Oxidative Modifications: a Potential Tool to Counteract Oxidative Stress in Neurodegenerative Diseases.

Advanced glycation end products (AGEs) are implicated in several central nervous system (CNS) pathologies including Alzheimer and Parkinson's diseases. In the face-off of AGE menace, we have attempted to investigate the zinc oxide nanoparticle (ZnONP) role in inhibition of AGE formation. Synthesized ZnONPs were used to investigate the inhibitory effects on AGE formation. The inhibitory effects of ZnONPs on AGE formation were determined by biophysical immunological and biochemical techniques. The results showed that ZnONP is a potential anti-glycating agent inhibiting AGE formation as well as protecting the protein structure from change. Therefore, our findings suggest ZnONPs may be used as a therapeutic in resolving the AGE role in CNS-related complications.

Synthesis, crystal structure, molecular docking studies and bio-evaluation of some N 4-benzyl-substituted isatin- 3-thiosemicarbazones as urease and glycation inhibitors

Abstract Fifteen N 4-benzyl-substituted isatin-3-thiosemicarbazones 5a–o were synthesized and evaluated for their urease and glycation inhibitory potential. Lemna aequinocitalis growth and Artemia salina assays were also done to determine their phytotoxic and toxic effects. All compounds are potent inhibitors of the urease enzyme, displaying inhibition [half maximal inhibitory concentration (IC50)=1.08±0.12–11.23±0.19 μm] superior to that of the reference inhibitor thiourea (IC50=22.3±1.12 μm). Compounds 5c, 5d, 5h, 5j,k are potent antiglycating agents, showing glycation inhibitory activity better than that of the reference inhibitor rutin (IC50 values 209.87±0.37–231.70±6.71 vs. 294.5±1.5 μm). In the phytotoxicity assay, 11 thiosemicarbazones 5a–d, 5g, 5h, 5j–l, 5n,o are active, demonstrating 5–100% growth inhibition of L. aequinocitalis at the highest tested concentrations (1000 or 500 μg/mL). In the brine shrimp (A. salina) lethality bioassay, three derivatives 5b, 5j and 5o are active with median lethal dose (LD50) values of 3.63×10−5, 2.90×10−5 and 2.31×10−4 m, respectively.