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The dried leaves of Melastoma malabathricum L. , locally named Karamunting or Senduduk, is traditionally consumed in many regions in Indonesia as herbal tea to cure different illnesses, including diabetes. To date, information on the compounds responsible for their antidiabetic activity is still very rare. The study aimed to identify bioactive compounds of M. malabathricum L. leaves using LC-MS based metabolomics and molecular docking approaches. The leaves brewed with different methods were subjected to LC−MS measurements and several bioactivity tests (in vivo and in vitro antihyperglycemic, and in vitro antioxidant). LC−MS data were linked to the activity data using multivariate data analysis. Molecular docking using alpha-glucosidase, alpha-amylase, and insulin receptor as protein targets was used to verify the results and study the interaction between the identified compound and protein targets. As results, isoquercetin and myricitrin were identified as compounds strongly associated with alpha-amylase inhibitors, while rutin and epicatechin were identified as alpha-glucosidase inhibitors. Quercitrin, citric acid, quercetin, epicatechin, isoquercitrin, and 7-hydroxycoumarine were strongly correlated with both antihyperglycemic and antioxidant activities. The results of metabolomics were confirmed with molecular docking studies, which showed that some of these compounds acted as competitive inhibitors, while others acted as non-competitive ones. Possible synergism between epicatechin and citric acid in their interaction with IR was detected. Metabolomics combined with molecular docking efficiently identified and confirmed several antihyperglycemic and antioxidant compounds from M. malabathricum L. , leaf. This study provides scientific evidence for the traditional use of M. malabathricum L. as an antidiabetic herbal. [ABSTRACT FROM AUTHOR]

The stem juices from Musa × paradisiaca L. banana plants cultivated in their original natural habitat in Vietnam and those cultivated in a greenhouse in the Czech Republic were investigated for the presence of phytochemicals with antidiabetic potency. Respective bioactivities of these phytochemicals were also determined. Sample screening using ultrahigh performance liquid chromatography coupled with tandem high-resolution mass spectrometry (UHPL-HRMS/MS) method showed some differences in the pattern of bioactive compounds, both in terms of their number and concentration. p-Hydroxybenzoic and gallic acids were the predominant analytes found in stem juice from plants grown in Vietnam, while ferulic acid was the major compound found in juice obtained from greenhouse bananas. Despite differences in the occurrence of potentially antidiabetic compounds, both extracts exhibited comparable inhibitory activity against α-glucosidase and α-amylase.

Deoxynojirimycin (DNJ) is the archetypal iminosugar, in which the configuration of the hydroxyl groups in the piperidine ring truly mimic those of d-glucopyranose; DNJ and derivatives have beneficial effects as therapeutic agents, such as anti-diabetic and antiviral agents, and pharmacological chaperones for genetic disorders, because they have been shown to inhibit α-glucosidases from various sources. However, attempts to design a better molecule based solely on structural similarity cannot produce selectivity between α-glucosidases that are localized in multiple organs and tissues, because the differences of each sugar-recognition site are very subtle. In this study, we provide the first example of a design strategy for selective lysosomal acid α-glucosidase (GAA) inhibitors focusing on the alkyl chain storage site. Our design of α-1-C-heptyl-1,4-dideoxy-1,4-imino-l-arabinitol (LAB) produced a potent inhibitor of the GAA, with an IC50 value of 0.44 µM. It displayed a remarkable selectivity toward GAA (selectivity index value of 168.2). A molecular dynamic simulation study revealed that the ligand-binding conformation stability gradually improved with increasing length of the α-1-C-alkyl chain. It is noteworthy that α-1-C-heptyl-LAB formed clearly different interactions from DNJ and had favored hydrophobic interactions with Trp481, Phe525, and Met519 at the alkyl chain storage pocket of GAA. Moreover, a molecular docking study revealed that endoplasmic reticulum (ER) α-glucosidase II does not have enough space to accommodate these alkyl chains. Therefore, the design strategy focusing on the shape and acceptability of long alkyl chain at each α-glucosidase may lead to the creation of more selective and practically useful inhibitors.

The Henry-type Barbier addition of bromonitromethane to 3-formylchromone, immediately followed by acetylation and concomitant elimination to afford nitroalkenes in excellent yield and total ( E )-selectivity is described. Cycloaddition of N -methylhydrazones with the obtained nitroalkenes gave the corresponding pyrazoles. Among the prepared pyrazoles, derivative 6j , which contains a catechol moiety, showed simultaneously a potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity and an α-glucosidase inhibitory activities. [ABSTRACT FROM AUTHOR]

Advancing age is the greatest single risk factor for numerous chronic diseases. Thus, the ability to target the aging process can facilitate improved healthspan and potentially lifespan. Lack of adequate glucoregulatory control remains a recurrent theme accompanying aging and chronic disease, while numerous longevity interventions result in maintenance of glucoregulatory control. In this review, we propose targeting glucose metabolism to enhance regulatory control as a means to ameliorate the aging process. We highlight that calorie restriction improves glucoregulatory control and extends both lifespan and healthspan in model organisms, but we also indicate more practical interventions (i.e., calorie restriction mimetics) are desirable for clinical application in humans. Of the calorie restriction mimetics being investigated, we focus on the type 2 diabetes drug acarbose, an α-glucosidase inhibitor that when taken with a meal, results in reduced enzymatic degradation and absorption of glucose from complex carbohydrates. We discuss alternatives to acarbose that yield similar physiologic effects and describe dietary sources (e.g., sweet potatoes, legumes, and berries) of bioactive compounds with α-glucosidase inhibitory activity. We indicate future research should include exploration of how non-caloric compounds like α-glucosidase inhibitors modify macronutrient metabolism prior to disease onset, which may guide nutritional/lifestyle interventions to support health and reduce age-related disease risk. [ABSTRACT FROM AUTHOR]

Even though the impurity analysis of the Ph. Eur. is considered well-studied, its methodology should be reviewed periodically to ensure that it is working properly, and all impurities are captured by the section „Related substances" of the monograph. Within this study, the biotechnological produced antidiabetic drug acarbose was chosen to demonstrate some of the advantages as well as the shortcomings arising from the current related substances test of acarbose. Due to its weak chromophore, acarbose is studied by UV detection at 210 nm after being separated on aminopropyl-silyl stationary phases. Thus, the use of alternative detection techniques, such as charge aerosol detection (CAD) and a volatile mobile phase can be beneficial here. Since a simple method transfer to a mobile phase usable with the CAD was not possible, more stable stationary phases were tested. For the rapid determination of the sum of impurities, a method was developed using a pentafluorophenyl column and a mobile phase of 0.1% TFA in water. Maltose and maltotriose were further identified as additional impurities of the API. Furthermore, a method was developed and validated by means of an Amide-HILIC phase, that adequately separated acarbose and all of its impurities. However, the sensitivity of this method needs to be further improved. Additionally, a method was also developed and validated, taking into account the temperature stability of graphite columns. Thus, the separation was carried out at temperatures of about 90 °C to solve the problem of anomerization of acarbose and some of its impurities. In comparison with the other developed methods, the elution order was changed and has to be confirmed, but all components were separated and detected at a sufficient LOQ of 0.10%. • Development and validation of new HPLC CAD methods for the impurity control of acarbose. • Impurity profiling of acarbose on different stationary phases. • Separation and detection of acarbose and its impurities by an Amide-HILIC column. • Alternative separation of acarbose and its impurities on a graphite column. [ABSTRACT FROM AUTHOR]

Although multivalent glucosidase inhibitors based on iminosugars have shown enhanced inhibition activity, an effective way to improve their hypoglycemic effect in vivo , is still in infancy and needs further development. In this paper, PBI-5DNJ and PBI-6DNJ , with three or four DNJ moieties respectively conjugated at the bay position were synthesized. PBI-6DNJ evidenced stronger π-π stacking interactions and, when self-assembled, a smaller size than that of PBI-5DNJ. It was found that PBI-6DNJ exhibited superior α-glucosidases (from mice) inhibition activity (K i = 0.14 ± 0.007 μM) in vitro than that (K i = 0.31 ± 0.01) of PBI-5DNJ and in vivo hypoglycemic effects in mice models. PBI-6DNJ possessed good hypoglycemic effects with the percentages of PBG levels of 40.40 ± 3.33% and 39.23 ± 4.84% at a dose of 2.0 mg/kg after 15 min and 30 min of administration, respectively. In terms of measuring percentage decrease of PBG level per DNJ unit, PBI-6DNJ displayed a 2.1-fold enhancement than miglitol, demonstrating a consistency between in vitro and in vivo experiments. This paves the way to the connection between in vivo hypoglycemic potency and in vitro glucosidase inhibition assay, leading to reliable and simplified assessment of hypoglycemic potency determination, and opening a basic understanding of the design of multivalent glucosidase inhibitors. [Display omitted] • PBI-6DNJ is a potent multivalent glycosidase inhibitor. • α-Glucosidase (from mice) inhibition activity guide development of the design of multivalent glucosidase inhibitors. • Self-assembly behaviors influence the glycosidase inhibition activity and hypoglycemic effects. • Multivalency was a strategy to improve glycosidase inhibition activity. [ABSTRACT FROM AUTHOR]

Affinity chromatography of specific enzymes is limited by the presence of related enzymes and the limited selectivity of the affinity ligand. We synthesized and investigated the use of an uncompetitive inhibitor as an affinity ligand, to leverage its three-component interactions. Use of the potent α-glucosidase uncompetitive inhibitor 2-aminoresorcinol as the ligand of the affinity gel offered selective purification of maltase-glucoamylase complex from the crude mixture of intestinal α-glucosidases. [ABSTRACT FROM AUTHOR]

Abstract: A simple and efficient synthesis of 1,4-dideoxy-1,4-imino-d-ribitol, 1,4-dideoxy-1,4-imino-l-lyxitol, N-benzyl derivative of d-ribitol, 3,4,5-trihydroxy-piperidine, l-4-epi-isofagomine and d-3-epi-isofagomine, which are glycosidase inhibitors has been described from the commercially available d-ribose as a starting material. [Copyright &y& Elsevier]

Azadirachta indica, used in antidiabetic herbal drugs, was reported to contain α-glucosidase inhibitor. Bioassay guided purification characterized the inhibitor as nimbidiol (a diterpenoid), present in root and stem-bark of the tree. Nimbidiol inhibited intestinal (mammalian) maltase-glucoamylase, sucrase-isomaltase, lactase, trehalase and fungal α-glucosidases. Nimbidiol showed a mixed competitive inhibition on intestinal carbohydrases. IC50, Ki and Ki′ (µM) were 1.35 ± 0.12, 0.08 ± 0.01, 0.25 ± 0.11, respectively, for maltase-glucoamylase (maltotetraose as substrate). Nimbidiol was more potent inhibitor of isomaltase (IC50 0.85 ± 0.035 µM), lactase (IC50 20 ± 1.33 µM) and trehalase (IC50 30 ± 1.75 µM) than acarbose, voglibose, salacinol, kotalanol and mangiferin. Ki and Ki′ values (µM) for intestinal sucrase were 0.7 ± 0.12 and 1.44 ± 0.65, respectively. Development of nimbidiol as an antidiabetic drug appears to be promising because of broad inhibition spectrum of intestinal glucosidases and easy synthesis of the molecule. [ABSTRACT FROM AUTHOR]

Highlights: [•] Three new phenylpropanoyl amides were isolated from leaves of Piper sarmentosum. [•] Chaplupyrrolidones A and B have new pyrrolidone moieties first reported in nature. [•] Chaplupyrrolidone B showed α-glucosidase inhibition equipotent as acarbose. [•] Mechanism underlying the inhibition was noncompetitive. [Copyright &y& Elsevier]

Background: Beta-glucosidase inhibitors are being extensively studied for use as anti-diabetics, anti-obesity and anti-tumour compounds. So far, these compounds have been reported in large numbers from plants, mushrooms, algae and fungi. There are very few reports of such inhibitors from bacteria in the open literature, particularly marine bacteria; although the best known inhibitor deoxynojirimycin was isolated from bacilli and actinomycete. Through this study, we tried to discover the diversity of microbial associates of marine sponge and sediment producing β-glucosidase inhibitors. Results: We found 41 (22.7%) out of 181 bacteria, produced such inhibitors. The inhibitors are abundant in bacterial associates of marine sponge Aka coralliphaga. When these bacteria were phylogenetically analyzed, it was found that marine bacteria producing glucosidase inhibitors belong to the phylum Firmicutes (23), Actinobacteria (9), Proteobacteria (7) and Bacteroidetes (1). Conclusion: A significant number of marine bacteria belonging to a wide range of bacterial taxa were found to produce β-glucosidase inhibitors. These compounds are abundantly present in bacteria of the phylum Firmicutes followed by the phylum Actinobacteria. The results nurture a hope of finding new compounds, which can inhibit glucosidases, in the bacterial domain of marine organisms. Thus, marine microbial cells can be utilized as producers of pharmacologically essential enzyme inhibitors. [ABSTRACT FROM AUTHOR]

Background: Few beta-glucosidase inhibitors have so far been reported from microorganisms due to the practical difficulties in performing the inhibition tests and subsequent interpretation of results. In an effort to investigate marine microbial extracts for ß-glucosidase inhibitors, we developed a new protocol, using esculin as substrate in an agar plate based assay, to screen a large number of microbial extracts in a short span of time. Results: With the new method, pale yellowish zones against the blackish brown background could be visually observed with more clarity in sample extracts where ß-glucosidase inhibitor was present. The new method was compared with the closest existing method and established beyond doubt. This agar plate based procedure required about one hour for minimum 12 samples and the throughput increases with the size of the agar gel plate used. Conclusions: The new protocol was simple, rapid and effective in detecting beta-glucosidase inhibitors in microbial extracts. [ABSTRACT FROM AUTHOR]

Abstract: The objectives of this study were to identify novel peptides from albumin, and to evaluate and validate the anti-diabetic activity of peptides against α-glucosidase and α-amylase. In the research, albumin hydrolysate was purified and identified, tandem MS was adapted to characterise the amino acid sequences of peptides from the hydrolysate. In addition, anti-diabetic effects of the peptides with α-glucosidase and α-amylase inhibitory activity have been performed. The present work found eight novel peptides from albumin. Results also suggested that peptide KLPGF had α-glucosidase inhibitory activity with an IC50 of 59.5±5.7μmoll−1 and α-amylase inhibitory activity with an IC50 of 120.0±4.0μmoll−1. In conclusion, the results revealed that the peptide KLPGF was a potential anti-diabetic inhibitor. [Copyright &y& Elsevier]

Abstract: Enzymes involved in N-glycan processing are targets of interest in the inhibition of host processes for the blockade of dengue virus (DENV) morphogenesis. Of the ten proteins encoded by DENV, three have N-glycosylation sites, namely pre-membrane/membrane protein (prM/M), envelope protein (E) and non-structural protein-1 (NS1). It is known that aberrations in the oligosaccharide portions at these N-glycan sites affect proper folding of these proteins during the translation process that, in turn, affects the morphogenesis of the budding DENV. Here we report on the testing for antiviral activity of four known sulfonium-ion α-glucosidase inhibitors and two 5-thiomannosylamine disaccharide derivatives against DENV. Two of the sulfonium ions tested, namely, kotalanol and its de-O-sulfonated derivative, naturally occurring potent intestinal α-glucosidase inhibitors, had comparable inhibitory activity [50% inhibitory concentration (IC50)=25.1±13.1μM and 50.4±8.6μM, respectively] with that of ribavirin (IC50 =25.2±8.3μM), a commercially available antiviral agent. The 5-thiomannosylamines did not show any activity at the concentrations tested. [Copyright &y& Elsevier]

Abstract: Inhibitors of α-amylase have attracted attention for their putative effects against diabetes mellitus. Although numerous studies have explored natural small molecule inhibitors, acarbose is currently the only compound with sufficient inhibitory potency and drug-like characteristics to be considered as a potential therapeutic agent. We have synthesized conjugates of the potent glucosidase inhibitor, 1-deoxynojirimycin, and glucose, with the aim of enhancing inhibitory activity against α-amylase. This synthetic conjugate showed increased inhibition of α-amylase compared to 1-deoxynojirimycin alone, suggesting that similar modifications of existing glucosidase inhibitors may yield more potent α-amylase inhibitors. [Copyright &y& Elsevier]

Abstract: Cyclization by double reductive amination of d-xylo-hexos-5-ulose with methyl 6-aminohexanoate gave (methoxycarbonyl)pentyl-1-deoxynojirimycin. Reaction of the terminal carboxylic acid with N-dansyl-1,6-diaminohexane provided the corresponding chain-extended fluorescent derivative. By reaction with bis(6-dansylaminohexyl)amine, the corresponding branched di-N-dansyl compound was obtained. Both compounds are strong inhibitors of d-glucosidases and could also be shown to distinctly improve, at sub-inhibitory concentrations, the activity of β-glucocerebrosidase in a Gaucher fibroblast (N370S) cell-line through chaperoning of the enzyme to the lysosome. [Copyright &y& Elsevier]

Abstract: CuI-catalysed azide alkyne 1,3-dipolar cycloaddition (CuAAC) ‘click chemistry’ was used to assemble a library of 21 α-d- and β-d-glucopyranosyl triazoles, which were assessed as potential glycosidase inhibitors. In the course of this work, different reactivities of isomeric α- and β-glucopyranosyl azides under CuAAC conditions were noted. This difference was further investigated using competition reactions and rationalised on the basis of X-ray crystallographic data, which revealed significant differences in bond lengths within the azido groups of the α- and β-anomers. Structural studies also revealed a preference for perpendicular orientation of the sugar and triazole rings in both the α- and β-glucosyl triazoles in the solid state. The triazole library was assayed for inhibition of sweet almond β-glucosidase (GH1) and yeast α-glucosidase (GH13), which led to the identification of a set of glucosidase inhibitors effective in the 100μM range. The preference for inhibition of one enzyme over the other proved to be dependent on the anomeric configuration of the inhibitor, as expected. [Copyright &y& Elsevier]

Tinospora cordifolia, used in anti-diabetic herbal drug preparations, was reported [12] to contain an α-glucosidase inhibitor, characterized as saponarin (apigenin-6-C-glucosyl-7-O-glucoside). The leaf extract had appreciable antioxidant and hydroxyl radical scavenging activities and contained the flavonoid in the range of 32.1 ± 1.5–45.5 ± 3.5 mg/g of dry solid. Saponarin showed mixed competitive inhibition on activities of α-glucosidase and sucrase of different origins. IC50, Ki and ki′ values determined were 48 μM, 8 μM and 19.5 μM respectively for intestinal maltase and 35 μM, 6 μM and 13 μM respectively for intestinal sucrase. When given orally to maltose-fed rat, saponarin showed hypoglycemic activity in the range of 20–80 mg/kg compared to 100–200 mg/kg for acarbose as reported [27]. [ABSTRACT FROM AUTHOR]

Abstract: Inhibitors of alpha glucosidases prevent the trimming of oligosaccharides on certain nascent glycoproteins, including the hepatitis B virus MHBs envelope glycoprotein. MHBs proteins with untrimmed oligosaccharides do not interact with calnexin, increasing protein misfolding and subsequent degradation by proteasomes. As peptides loaded onto newly synthesized MHC class I complexes are predominantly derived from proteasomes, the possibility that glucosidase inhibition could increase presentation by MHC class I was determined. Using either a model epitope, or a natural MHBs epitope, it was demonstrated that glucosidase inhibitors enhanced presentation by MHC class I and promoted activation of antigen-specific CTLs, suggesting a pharmacologic approach to immune modulation. [Copyright &y& Elsevier]

Abstract: Andrographolide (1), the cytotoxic agent of the plant Andrographis paniculata, was subjected to semi-synthetic studies leading to a series of new derivatives, a novel family of glucosidase inhibitors. Nicotination of 3,19-hydroxyls in 15-alkylidene andrographolide derivatives (9) was favorable to α-glucosidase inhibition activity. Among them, 15-p-chlorobenzylidene-14-deoxy-11,12-didehydro-3,19-dinicotinateandrographolide (11c) was a very potent inhibitor against α-glucosidase with an IC50 value of 6μM. However, all compounds concerned for β-glucosidase showed no inhibition. All compounds synthesized were characterized by the analysis of NMR, IR, HRMS spectra and the stereochemistry of 2 was confirmed by X-ray analysis. [Copyright &y& Elsevier]

Abstract: Valienamine is an important medicinal intermediate with broad use in the synthesis of some stronger α-glucosidase inhibitors. In order to improve valienamine concentration in the fermentation broth and make the downstream treatment easy, a fed-batch process for the enhanced production of valienamine by Stenotrophomonas maltrophilia in a stirred tank bioreactor was developed. Results showed that supplementation of validamycin A in the process of cultivation could increase the valienamine concentration. One-pulse feeding was observed to be the best strategy. The maximum valienamine concentration of 2.35gL−1 was obtained at 156h when 86.4g of validamycin A was added to a 15-L bioreactor containing 8L fermentation medium with one-pulse feeding. The maximum valienamine concentration had a great improvement and was increased above 100% compared to batch fermentation in the stirred tank bioreactor. The pH-controlled experiments showed that controlling the pH in the process of one-pulse feeding fermentation had not obvious effect on the production of valienamine. [Copyright &y& Elsevier]

Aims: To isolate, identify and assess valienamine production by a soil bacterial isolate from a wheat field in Hangzhou, China. Methods and Results: A validamycin A-degrading bacterial strain, numbered ZJB-041, was isolated and identified as Stenotrophomonas maltophilia, based on morphology, physiological tests, ATB system (ID32 GN), and 16S rDNA analysis. The strain was capable of producing valienamine by decomposing validamycin A. After fermentation in shaking flasks at 30°C for 7 days, 96·0% of 34·49 mmol l−1 of validamycin A was degraded and 2·65 mmol l−1 of valienamine was obtained. The resting cells of this strain also produced valienamine by degrading validamycin A. After 72 h of incubation in 0·2 mol l−1 of phosphate buffer (pH 7·5), 90·2% of 17·16 mmol l−1 of validamycin A was degraded, and 1·77 mmol l−1 of valienamine was obtained. Conclusions: Our data suggested that S. maltophilia ZJB-041, a bacterial isolate, has the potential for validamycin A degradation and valienamine production. Significance and Impact of the Study: The validamycin A-degrading bacterium could potentially be utilized in the disposal of validamycin residues and in the production of valienamine. [ABSTRACT FROM AUTHOR]

Abstract: Glycoside trimming enzymes are crucially important in a broad range of metabolic pathways, including glycoprotein and glycolipid processing and carbohydrate digestion in the intestinal tract. Amongst the large array of enzymes, glucosidases are postulated to be a powerful therapeutic target since they catalyze the cleavage of glycosidic bonds releasing glucose from the non-reducing end of an oligo- or polysaccharide chain involved in glycoprotein biosynthesis. Glucosidase inhibitors are currently of interest owing to their promising therapeutic potential in the treatment of disorders such as diabetes, human immunodeficiency virus (HIV) infection, metastatic cancer, and lysosomal storage diseases. Glucosidase inhibitors have also been useful in probing biochemical pathways and understanding structure–activity relationship patterns required for mimicking the enzyme transition state. Amongst the various types of glucosidase inhibitors, disaccharides, iminosugars, carbasugars, thiosugars, and non-sugar derivatives have received great attention. This review is aimed at highlighting the main chemical classes of glucosidase inhibitors, as well as their biological activities toward α- and β-glucosidases, but it is not intended to be an exhaustive review on the subject. Inhibition data on the compounds covered in this review are included in a tabular form as an Appendix, where the type of each glucosidase associated with a specific inhibitor is also given. [Copyright &y& Elsevier]

Abstract: Based on our extensive studies of d-glucosidase inhibiting 2,5-dideoxy-2,5-imino-d-mannitol derivatives, we have been trying to create a series of fluorescent derivatives with a view to an ‘inhibitory activity ruler’ based on competitive displacement reactions of non-fluorescent inhibitors by fluorescent ones and vice versa, which can be performed and followed in microtiter plates or on-chips. Thus, a set of compounds was assembled with K i values between 2nM and 1μM against Agrobacterium sp. β-glucosidase. [Copyright &y& Elsevier]

Recently, it was shown that replication of bovine viral diarrhea virus (BVDV) is sensitive to inhibitors of host ER glucosidases. Consistent with these findings, we report that incubation of BVDV-infected MDBK cells with the glucosidase inhibitor n-butyl-deoxynojirimycin (nB-DNJ) reduced BVDV yields by 70- to 100-fold (n = 27), while having no effect on MDBK cell viability. However, the 70- to 100-fold reduction in infectious virus was associated with only a 2-fold reduction in genomic RNA synthesis and secretion of enveloped virus particles. Analysis of secreted virions showed that in the absence of glucosidase inhibitor, approximately 50% of the virion-associated BVDV E2 glycoprotein was resistant to endoglycosidase H (endo H) digestion, whereas intracellular E2 was completely sensitive to endo H digestion. In the presence of glucosidase inhibitor, virion-associated E2 and intracellular E2 were completely sensitive to endo H digestion. Taken together, these results suggest that BVDV is secreted through a Golgi-mediated pathway and that host ER glucosidase activity is required for production of infectious virions and Golgi processing of envelope E2 protein during virus egress. [Copyright &y& Elsevier]

The absorbable deoxynojirimycin derivative emiglitate (BAY o 1248) is a potent competitive inhibitor of small intestinal α-glucosidases in man. In two similar randomized, placebo-controlled, double blind investigations, the efficacy, duration of action and tolerability of single doses of 10, 20 and 40 mg emiglitate have been assessed in healthy male volunteers after repeated sucrose or maize-starch loads at 08.00, 12.00 and 17.00 h. Even at the lowest dose used, emiglitate almost abolished the glycaemic (−88%) and hormonal responses after the first sucrose meal, simultaneously evoking significant hydrogen evolution (mean peak H-concentration >100 ppm), which was not related to the dose, and which induced unacceptable symptoms of carbohydrate malabsorption, i.e. at the dosages tested, the inhibition of glycaemic and hormonal responses was at the expense of intolerable gastrointestinal adverse effects. Flattening of postprandial responses of blood glucose, serum insulin and gastric inhibitory polypeptide was still apparent after a second sucrose load 4 h later, demonstrating long-lasting inhibition of α-glucosidase activity. After starch, the dose dependency of inhibition emerged more clearly than after sucrose, i.e. the reduction was less pronounced. However, emiglitate led to significant reduction of the glycaemic and hormonal rises after both the first and second starch meals. Symptoms of carbohydrate malabsorption were absent after 10 mg and were negligible with 20 mg or 40 mg emiglitate. Breath hydrogen concentration increased gradually, indicating slight but significant carbohydrate malabsorption after the highest dose of the α-glucosidase inhibitor. The results show that a single morning dose of 20-40 mg emiglitate might be useful in the control of postprandial hyperglycaemia after breakfast and lunch. This dose of the inhibitor was effective after either both 50 g starch or 50 g sucrose as the substrate, but was only tolerable after the starch meal. [ABSTRACT FROM AUTHOR]

The article discusses synthesis and intestinal glucosidase enzyme inhibiting activity of 2-Aminoresorcinol that is a potent and selective intestinal glucosidase inhibitor. It reports that mechanism of action of 2-Aminoresorcinol for inhibition of glucosidase enzyme is achieved through structural changes in amino acids and hydroxylation of two phenolic hydroxyl groups. It suggest design of a molecular probe for study of inhibition mechanism of 2-Aminoresorcinol.

Abstract: Dengue virus infection causes diseases in people, ranging from the acute febrile illness dengue fever, to life-threatening dengue hemorrhagic fever/dengue shock syndrome. We previously reported that a host cellular α-glucosidases I and II inhibitor, imino sugar CM-10–18, potently inhibited dengue virus replication in cultured cells, and significantly reduced viremia in dengue virus infected AG129 mice. In this report we show that CM-10–18 also significantly protects mice from death and/or disease progress in two mouse models of lethal dengue virus infection. Our results thus provide a strong support for the development of CM-10–18 or its derivatives as antiviral agents to treat servere dengue virus infections. [Copyright &y& Elsevier]

• A new series of pyridazine-based compounds were synthesized as glucosidase inhibitors. • The most active compound was 10 times more active than acarbose. • Kinetic and molecular docking studies were performed to determine the mode of inhibition. We herein applied the four step-synthetic route to prepare the pyridazine core attached to the various N -aryl acetamides. By this approach, a new series of pyridazine-based compounds were synthesized, characterized and evaluated for their activities against α-glucosidase enzyme. In - vitro α-glucosidase assay established that twelve compounds are more potent than acarbose. Compound 7a inhibited α-glucosidase with the IC 50 value of 70.1 µM. The most potent compounds showed no cytotoxicity against HDF cell line. Molecular docking and kinetic studies were performed to determine the modes of interaction and inhibition, respectively. [ABSTRACT FROM AUTHOR]