Potent Α-glucosidase Inhibitors Research Articles

Synthesis of Competitive and Noncompetitive Inhibitors of Alpha-Glucosidase and Anticancer Agents.

Imidazoles and phenylthiazoles are an important class of heterocycles that demonstrate a wide range of biological activities against various types of cancers, diabetes mellitus and pathogenic microorganisms. The heterocyclic structure having oxothiazolidine moiety is an important scaffold present in various drugs, with potential for enzyme inhibition. In an effort to discover new heterocyclic compounds, we synthesized 26 new 4,5-diphenyl-1H-imidazole, phenylthiazole, and oxothiazolidine heterocyclic analogues that demonstrated potent α-glucosidase inhibition and anticancer activities. Majority of the compounds noncompetitively inhibited α-glucosidase except for two that exhibited competitive inhibition of the enzyme. Docking results suggested that the noncompetitive inhibitors bind to an apparent allosteric site on the enzyme located in the vicinity of the active site. Additionally, the analogues also exhibited significant activity against various types of cancers including non-small lung cancer. Since tubulin protein plays an important role in the pathogenesis of non-small lung cancer, molecular docking with one of the target compounds provided important clues to its binding mode. The current work on imidazoles and phenylthiazole derivatives bears importance for designing of new antidiabetic and anticancer drugs.

Pyridazine derivative as potent antihyperglycemic agent: Synthesis, crystal structure, α-amylase and α-glucosidase inhibition and computational studies

In this study, a pyridazine derivative (PDZ-1) was synthesized and characterized by using 13C NMR, 1H NMR, FT-IR, UV–Vis, HRMS-ESI and single-crystal X-ray diffraction analysis (XRD). Density functional theory methods at the B3LYP/6–311++G** level of theory predict very good correlations in the geometrical parameters and spectra when they are compared with the corresponding experimental ones. The presence of dimer explains the broad IR band due to CH···O interactions. The scaled force constants and the 75 vibration modes of PDZ-1 have been completely assigned using the scaled quantum mechanical force field (SQMFF) methodology. The deactivating character of Cl atom probably explains that the densities of pyridazine rings in both media are higher than that corresponding to chlorobenzyl, as revealed by AIM study while NBO calculations show that the derivative is most stable in gas phase than ethanol solution. Frontier orbital studies reveal that PDZ-1 is most reactive in ethanol than in the gas phase. The title compound showed a potent α-glucosidase and α-amylase inhibition compared to Acarbose (IC50 = 113.6 ± 1.17 µM, 124.5 ± 0.64 µM, respectively) with IC50 values of 17.32 ± 0.76 and 109.41± 0.87 µM, respectively. In addition, molecular docking studies were performed to determine the binding modes and energies between PDZ-1 and the target enzymes.

Synthesis and characterization of some novel benzoyl thioureas as potent α-glucosidase inhibitors: In vitro and in silico

A series of sixteen benzoyl thiourea derivatives was prepared in good to excellent yield (49–92 %). Eight out of sixteen were reported compounds. The structures of prepared derivatives were elucidated by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic (1H NMR) and carbon nuclear magnetic resonance (13C NMR), and mass spectroscopy (ESI-MS). The structure of two compounds TU-8 and TU-15 was further established by single crystal X-ray diffraction (SCXRD) studies. All of the prepared compounds were screened for their potential as α-glucosidase inhibitor and found to be more potent than standard acarbose. TU-8 and TU-14 were lead compounds with IC50 values 1.59 ± 0.04 µM and 0.60 ± 0.02 µM, respectively. All the prepared compounds were found to non-toxic to fibroblast 3T3-L1 cell lines. The structure activity relation was confirmed by various substituents on phenyl ring. Furthermore, the interaction of compounds with enzyme was confirmed by docking studies. This study proves that synthesized 1, 3-disubstituted thiourea derivatives are excellent α-glucosidase inhibitor and can be exploited to design novel therapeutics to cure type-II diabetes.

PHARMACOLOGICAL AND BIOLOGICAL EVALUATION OF METHANOL EXTRACTS OF SELECTED CHOLISTANI PLANTS

Cholistani plants are a rich source of bioactive compounds that are helpful in treating various ailments. The objective of the current investigation was to elucidate the pharmacological importance of four Cholistani plants including L. indicum, E. granulata, C. prostratus, and H. crispum. Methanolic extracts of these plants were subjected to antibacterial, antibiofilm, antioxidant, antidiabetic, and antiviral analysis. Disc diffusion assay was used for antibacterial activity and the MIC of active extracts was also calculated. In vitro antibiofilm assay was conducted against drug-resistant and drug-sensitive bacterial strains and % inhibition was calculated. DPPH assay was used for the evaluation of antioxidant potential. The antidiabetic potential was tested by α-glucosidase inhibitory assay. The Haemagglutination (HA) test was performed to assess the antiviral properties of these plants against the Avian Influenza Virus (H9N2). It was found that E. granulata prevailed in antibacterial potential with max ZoI against selected bacterial strains (16.5 mm versus E. coli. C. prostratus) surpassed all other plant extracts in terms of biofilm inhibition with up to 90% inhibition against P. aeruginosa. Considerable antioxidant potential was revealed by all examined plants in the order of E. granulata> C. prostratus > L. indicum > H. crispum. A substantial α-glucosidase inhibitory potential was detected in all the studied plants. All of the examined plants displayed significant (titer 0) antiviral activity. This study reveals that all of these plants have the potential to be employed as antibacterial, antioxidant, and antiviral agents. In vitro suppression of the α-glucosidase enzyme indicated that these plants are potent sources of antidiabetic compounds. In conclusion, all of the examined Cholistani plants are rich sources of pharmacological compounds and should be further researched for drug development. Key words: E. granulata, C. prostratus, L. indicum, H. crispum, antibacterial, antioxidant, antibiofilm, antiviral

Synthesis,Antidiabetic and Antitubercular Evaluation of Quinoline-pyrazolopyrimidine hybrids and Quinoline-4-Arylamines.

Two libraries of quinoline-based hybrids 1-(7-chloroquinolin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine and 7-chloro-N-phenylquinolin-4-amine were synthesized and evaluated for their α-glucosidase inhibitory and antioxidant properties. Compounds with 4-methylpiperidine and para-trifluoromethoxy groups, respectively, showed the most promising α-glucosidase inhibition activity with IC50=46.70 and 40.84 μM, compared to the reference inhibitor, acarbose (IC50=51.73 μM). Structure-activity relationship analysis suggested that the cyclic secondary amine pendants and para-phenyl substituents account for the variable enzyme inhibition. Antioxidant profiling further revealed that compounds with an N-methylpiperazine and N-ethylpiperazine ring, respectively, have good DPPH scavenging abilities with IC50=0.18, 0.58 and 0.93 mM, as compared to ascorbic acid (IC50=0.05 mM), while the best DPPH scavenger is NO2-substituted compound (IC50=0.08 mM). Also, compound with N-(2-hydroxyethyl)piperazine moiety emerged as the best NO radical scavenger with IC50=0.28 mM. Molecular docking studies showed that the present compounds are orthosteric inhibitors with their quinoline, pyrimidine, and 4-amino units as crucial pharmacophores furnishing α-glucosidase binding at the catalytic site. Taken together, these compounds exhibit dual potentials; i. e., potent α-glucosidase inhibitors and excellent free radical scavengers. Hence, they may serve as structural templates in the search for agents to manage Type 2 diabetes mellitus. Finally, in preliminary assays investigating the anti-tubercular potential of these compounds, two pyrazolopyrimidine series compounds and a 7-chloro-N-phenylquinolin-4-amine hybrid showed sub-10 μM whole-cell activities against Mycobacterium tuberculosis.

Evaluation of novel 2-(quinoline-2-ylthio)acetamide derivatives linked to diphenyl-imidazole as α-glucosidase inhibitors: Insights from in silico, in vitro, and in vivo studies on their anti-diabetic properties

The inhibition of the α-glucosidase enzyme is crucial for targeting type 2 diabetes mellitus (DM). This study introduces a series of synthetic analogs based on thiomethylacetamide-quinoline derivatives linked to diphenyl-imidazole as highly potential α-glucosidase inhibitors. Twenty derivatives were synthesized and screened in vitro against α-glucosidase, revealing IC50 values ranging from 0.18 ± 0.00 to 2.10 ± 0.07 μM, in comparison to the positive control, acarbose. Among these derivatives, compound 10c (IC50 = 0.180 μM) demonstrated the highest potency and revealed a competitive inhibitory mechanism in kinetic studies (Ki = 0.15 μM). Docking and molecular dynamic evaluations elucidated the binding mode of 10c with the active site residues of the α-glucosidase enzyme. Moreover, in vivo assessments on a rat model of DM affirmed the anti-diabetic efficacy of 10c, evidenced by reduced fasting and overall blood glucose levels. The histopathological evaluation enhanced pancreatic islet architecture and hepatocytes in liver sections. In conclusion, novel 2-(quinoline-2-ylthio)acetamide derivatives as potent α-glucosidase inhibitors were developed. Compound 10c emerged as a promising candidate for diabetes management, warranting further investigation for potential clinical applications and mechanistic insights.

Evaluation on the Potential of Ganoderma lucidum Bioactive Compounds as Alpha Glucosidase Enzyme Inhibitor: A Computational Study

Introduction: Computational simulation study was carried out on bioactive compounds of Ganoderma lucidum (G. lucidum). Methods: Molecular docking and molecular dynamics (MD) simulations were performed. The input files for protein and ligands were retrieved from Protein Data Bank (PDB) and PubChem database. Human maltase-glucoamylase (PDB ID: 3L4Y) is the protein (α-glucosidase enzyme). The ligands are thirteen compounds derived from G. lucidum together with acarbose and miglitol as controls. Results: Docking result showed the lowest binding energy is from Ganomycin B (-7.8 kcal/mol) compared to acarbose and miglitol (-5.0 kcal/mol and -4.4 kcal/mol) respectively. MD simulation showed interaction of 3L4Y-Ganomycin B achieved stable interaction and conformation as follows: root mean square deviation (RMSD) is ± 2.7 Å, average distance of ±1.8 Å and constant hydrogen bonds around 1 - 3. Conclusion: Ganomycin B was found to have good binding affinity, embarking its potential as a potent α-glucosidase inhibitor.

α-Glucosidase Inhibitory Activity of Tea and Kombucha from Rhizophora mucronata Leaves

A decoction of Rhizophora mucronata Lam. mangrove bark is used as an antidiabetic treatment in Asia. Kombucha tea is a fermented beverage, which is also claimed to be antidiabetic. In this work, the potency of R. mucronata leaves as α-glucosidase inhibitor was studied to assess whether it could be a suitable alternative to the use of R. mucronata bark. α-glucosidase inhibitory activities were determined for three extracts prepared from R. mucronata leaves, being the unfermented tea of R. mucronata leaves, the fermented kombucha tea and an 80% methanolic extract of the residual R. mucronata leaves. Flavonoid glycosides were identified in tea powder, kombucha tea and in the crude methanolic extract. Both the unfermented tea and the kombucha tea after 7 days of fermentation inhibited α-glucosidase with IC50 values of 0.12 ± 0.02 mg/mL and 0.09 ± 0.04 mg/mL, respectively. The methanolic extract showed a stronger α-glucosidase inhibitory activity compared to the kombucha tea and tea powder with an IC50 value of 0.0435 ± 0.0007 mg/mL. Acarbose, used as a positive control, inhibited α-glucosidase with an IC50 value of 2.4 ± 0.2 mg/mL. It was found that the three types of preparations of R. mucronata all were potent α-glucosidase inhibitors.

Chemical characterization of different parts of Forsythia suspensa and α-glucosidase and pancreatic lipase inhibitors screening based on UPLC-QTOF-MS/MS and plant metabolomics analysis

Forsythia suspensa (Thunb.) Vahl (FS) is an important plant with high edible and medicinal values. The edible fruit of FS is a common traditional medicine in China, Japan and Korea. Compared to the research on the phytochemistry and pharmacology of the fruits, study on the other parts of FS, such as leaves and flowers is still limited. In this study, an integrated strategy based on ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF-MS/MS), plant metabolomics and correlation analysis was established for comprehensively chemical characterization of fruits, leaves and flowers of FS, and discovery of α-glucosidase and pancreatic lipase inhibitory metabolites. The plant metabolic profiling of fruits, leaves and flowers of FS was performed by UPLC-QTOF-MS/MS, and a total of 74 secondary metabolites, including 15 phenylethanoid glycosides, 20 lignans, 10 cyclohexanol derivatives, 11 organic acids, 9 flavonoids, 3 triterpenes, and 10 other compounds were identified. Then, 29 differential secondary metabolites that responsible to distinguish the fruits, leaves and flowers of FS were further screened out by multivariate statistical analysis. Meanwhile, the α-glucosidase and pancreatic lipase inhibition of different parts of FS were evaluated and compared by in vitro experiments. The results demonstrated that the leaves of FS showed the highest inhibition on α-glucosidase and pancreatic lipase with IC50 of 0.17 ± 0.04 mg/mL and 0.56 ± 0.33 mg/mL, respectively. Then, the correlation between differential metabolites and enzyme inhibitory activities were investigated by Pearson correlation analysis, and 12 potential α-glucosidase and pancreatic lipase inhibitors were screen out. Additionally, the α-glucosidase and pancreatic lipase inhibitory activities of five potential enzyme inhibitory components, including quercitrin, rutin, kaempferol-3-O-rutinoside, pinoresinol-4-O-glucoside and phillyrin were further validated by in vitro assays and molecular docking analysis. The results showed that all the five potential inhibitors showed good inhibitory effects on α-glucosidase and pancreatic lipase, and the binding of the five inhibitors to enzymes mainly through hydrogen bonding, hydrophobic force, and ionic bonding. This study provided a feasible strategy for comparison and discrimination of different parts of medicinal plant and discovery of bioactive components, and also provided useful information for future utilization of different parts of FS.

Synthesis and Biological Evaluation of New Dihydrofuro[3,2-b]piperidine Derivatives as Potent α-Glucosidase Inhibitors.

Inhibition of glycoside hydrolases has widespread application in the treatment of diabetes. Based on our previous findings, a series of dihydrofuro[3,2-b]piperidine derivatives was designed and synthesized from D- and L-arabinose. Compounds 32 (IC50 = 0.07 μM) and 28 (IC50 = 0.5 μM) showed significantly stronger inhibitory potency against α-glucosidase than positive control acarbose. The study of the structure-activity relationship of these compounds provides a new clue for the development of new α-glucosidase inhibitors.

Chemical Constituents, Hypolipidemic, and Hypoglycemic Activities of Edgeworthia gardneri Flowers.

The flowers of Edgeworthia gardneri are used as herbal tea and medicine to treat various metabolic diseases including hyperglycemia, hypertension, and hyperlipidemia. This paper investigate the chemical constituents and biological activities of ethanolic extract and its different fractions from E. gardneri flowers. Firstly, the E. gardneri flowers was extracted by ethanol-aqueous solution to obtain crude extract (CE), which was subsequently fractionated by different polar organic solution to yield precipitated crystal (PC), dichloromethane (DCF), ethyl acetate (EAF), n-butanol (n-BuF), and residue water (RWF) fractions. UHPLC-ESI-HRMS/MS analysis resulted in the identification of 25 compounds, and the main compounds were flavonoids and coumarins. The precipitated crystal fraction showed the highest phenolic and flavonoid contents with 344.4 ± 3.38mg GAE/g extract and 305.86 ± 0.87mg RE/g extract. The EAF had the strongest antioxidant capacity and inhibitory effect on α-glucosidase and pancreatic lipase with IC50 values of 126.459 ± 7.82 and 23.16 ± 0.79 µg/mL. Besides, both PC and EAF significantly regulated the glucose and lipid metabolism disorders by increasing glucose consumption and reducing TG levels in HepG2 cells. Molecular docking results suggested that kaempferol-3-O-glucoside and tiliroside had good binding ability with enzymes, indicating that they may be potential α-glucosidase and pancreatic lipase inhibitors. Therefore, the E. gardneri flowers could be served as a bioactive agent for the regulation of metabolic disorders.

Antioxidant and α-Glucosidase inhibitory activity of various solvent fractions from Amaranthus viridis L., Amaranthus tricolor L., and Amaranthus spinosus L.

Amaranthus tricolor L., Amaranthus spinosus L., and Amaranthus viridis L. are well-known for flavoring food products and traditional medicine. This study investigated the antioxidant and α-glucosidase inhibitory activity of various solvent fractions from the whole plant of A. tricolor, A. spinosus, and A. viridis in Vietnam. The total extract and solvent fractions of petroleum ether (PE), chloroform (CF), ethyl acetate (EA), n-butanol (B), and water (W) were tested for antioxidant activity using the DPPH assay and α-glucosidase inhibition. The results showed that the three species of Amaranthus had relatively low antioxidant activity, and the total extract of A. spinosus L. had the highest antioxidant activity with an IC50 value of 324.96 μg/mL. The EA fraction of A. tricolor had outstanding α-glucosidase inhibitory activity with an IC50 value of 95.94 μg/mL. It is recommended to continue isolation research to find active ingredients with α-glucosidase inhibition potential in the EA extract of A. tricolor. Additionally, an in vivo assay might be conducted to evaluate the activity and toxicity of this EA fraction.

Nicotinonitriles as potential inhibitors of α-glucosidase, tyrosinase, and urease enzymes: Synthesis, characterization, in vitro, and in silico studies

In an effort to develop novel enzyme inhibitors with potent activity and high selectivity, a series of nicotinonitrile derivatives was synthesized. Cyano pyridone intermediates undergo nucleophilic substitution reactions with variously substituted phenacyl halides to yield the nicotinonitriles 1–20. All nicotinonitriles exhibited moderate to excellent in vitro enzyme inhibitory activities against α-glucosidase, tyrosinase, and urease. Compound 1 (IC50 = 27.09 ± 0.12 µM) selectively displayed more significant activity than the standard acarbose (IC50 = 40.00 ± 0.70 µM). Compound 1 also showed good urease inhibition (IC50 = 33.04 ± 0.70 µM); however, it exhibited activity less than the standard acetohydroxamic acid (IC50 = 27.00 ± 0.50 µM).Furthermore, the most effective compound of the series against tyrosinase compared to the standard kojic acid (IC50 = 16.9 ± 1.30 µM) was 16 with an IC50 value of 10.55 ± 0.08 µM. In contrast, this compound showed no activity against α-glucosidase and urease. DFT calculations were carried out to analyze electronic transitions and energy levels (HOMO and LUMO) in nicotinonitrile derivatives, offering insights into their chemical reactivity and stability. Molecular docking studies and molecular electrostatic potential (MEP) revealed the interactions of the active compounds with the amino acid residues at the active sites of the enzymes, thereby shedding light on the mechanism of enzyme inhibition. Therefore, compound 1 can be further studied as a promising α-glucosidase and urease inhibitor, while compound 16 is an effective tyrosinase inhibitor.

Thiazolidine-2,4-dione derivatives as potential α-glucosidase inhibitors: Synthesis, inhibitory activity, binding interaction and hypoglycemic activity

In order to find effective α-glucosidase inhibitors, a series of thiazolidine-2,4-dione derivatives (C1 ∼ 36) were synthesized and evaluated for α-glucosidase inhibitory activity. Compared to positive control acarbose (IC50 = 654.35 ± 65.81 μM), all compounds (C1 ∼ 36) showed stronger α-glucosidase inhibitory activity with IC50 values of 0.52 ± 0.06 ∼ 9.31 ± 0.96 μM. Among them, C23 with the best anti-α-glucosidase activity was a reversible mixed-type inhibitor. Fluorescence quenching suggested the binding process of C23 with α-glucosidase in a static process. Fluorescence quenching, CD spectra, and 3D fluorescence spectra results also implied that the binding of C23 with α-glucosidase caused the conformational change of α-glucosidase to inhibit the activity. Molecular docking displayed the binding interaction of C23 with α-glucosidase. Compound C23 (8 ∼ 64 μM) showed no cytotoxicity against LO2 and 293 cells. Moreover, oral administration of C23 (50 mg/kg) could reduce blood glucose and improve glucose tolerance in mice.

In silico Exploration of Pharmacological and Molecular Descriptor Properties of Salacinol and Its Related Analogues

Salacinol and its related analogues have been known for their potent α-glucosidase inhibitor activity and making them interesting candidates for a new type of anti-diabetic agent. Therefore, it is essential to investigate the physicochemical properties, pharmacological parameters, and toxicity profile of these anti-diabetic agents. In this study, a comprehensive in-silico approach was used to explore the absorption, distribution, metabolism, excretion, and toxicity profiles of salacinol and its related analogues. In addition, to gain a better knowledge of structural and electrical characteristics, global and local reactivity descriptors, and molecular electrostatic potential were calculated and discussed by using DFT at the B3LYP/6–311++G (d, p) level of theory. The results explored that all the studied compounds have low GI absorption and are substrates for P-glycoprotein. None of the compounds can cross the BBB, and none of the compounds are inhibitors of cytochrome P450 isoenzymes. We also found that all compounds have various potential to interact with a wide range of biological targets, including GPCRs, enzymes, ion channels, kinases, and nuclear receptors. Additionally, all compounds have low toxicity and are unlikely to cause any major health hazards in terms of hepatotoxicity, mutagenicity, cardiotoxicity, cytotoxicity, and immunotoxicity. The molecular electrostatic potential map shows that the negative potential sites are in electronegative oxygen atoms, while the positive potential sites are around the hydrogen atoms. The present study concludes that salacinol and its analogues might be a promising safe and effective candidate for the development of therapeutic drugs derived from natural sources. However, some of their properties should be considered in the context of drug development and tissue protection strategies.

Antioxidant and α-glucosidase inhibitory potential of the pollen of Hibiscus spp.

Antioxidant and α-glucosidase inhibitory potential of the pollen of Hibiscus spp.

New Garden Rose (Rosa × hybrida) Genotypes with Intensely Colored Flowers as Rich Sources of Bioactive Compounds

Garden roses, known as Rosa × hybrida, hold a prominent position as one of the most important and economically valuable plants in horticulture. Additionally, their products—essential oil, rose water, concrete, and concentrate—find extensive use in the cosmetic, pharmaceutical, and food industries, due to their specific fragrances and potential health benefits. Rose flowers are rich in biologically active compounds, such as phenolics, flavonoids, anthocyanins, and carotenoids. This study aims to investigate the potential of five new garden rose genotypes with intensely colored flowers to serve as sources of biologically active compounds. Phenolic profile was evaluated by determination of total phenolic (TPC), flavonoid (TFC), and monomeric anthocyanins (TAC) contents and LC-MS/MS analysis of selected compounds. Antioxidant activity was evaluated via DPPH and FRAP assays, neuroprotective potential via acethylcholinesterase inhibition assay, and antidiabetic activity viaα-amylase and α-glucosidase inhibition assays. The flowers of investigated genotypes were rich in phenolics (TPC varied from 148 to 260 mg galic acid eq/g de, TFC from 19.9 to 59.7 mg quercetin eq/g de, and TAC from 2.21 to 13.1 mg cyanidin 3-O-glucoside eq/g de). Four out of five genotypes had higher TPC than extract of R. damascene, the most famous rose cultivar. The dominant flavonoids in all investigated genotypes were glycosides of quercetin and kaempferol. The extracts showed high antioxidant activity comparable to synthetic antioxidant BHT, very high α-glucosidase inhibitory potential, moderate neuroprotective activity, and low potential to inhibit α-amylase.

In silico exploration of the potential inhibitory activities of in-house and ZINC database lead compounds against alpha-glucosidase using structure-based virtual screening and molecular dynamics simulation approach

Inhibitors of α-glucosidase have been used to treat type-2 diabetes (T2DM) by preventing the breakdown of carbohydrates into glucose and prevent enhancing glucose conversion. Structure-based virtual screening (SBVS) was used to generate novel chemical scaffold-ligand α-glucosidase inhibitors. The databases were screened against the receptor α-glucosidase using SBVS and molecular dynamics simulation (MDS) techniques in this study. Based on molecular docking studies, three and two compounds of α-glucosidase inhibitors were chosen from a commercial database (ZINC) and an In-house database for this study respectively. The mode of binding interactions of the selected compounds later predicted their α-glucosidase inhibitory potential. Finally, one out of three lead compound from ZINC and one out of two lead compound from In-house database were shortlisted based on interactions. Furthermore, MDS and post-MDS strategies were used to refine and validate the shortlisted leads along with the reference acarbose/α-glucosidase. The Hits’ ability to inhibit α-glucosidase was predicted by SBVS, indicating that these compounds have good inhibitory activities. The lead inhibitor’s structure may serve as templates for the design of novel inhibitors, and in vitro testing to confirm their anti-diabetic potential is necessary. These insights can help rationally design new effective anti-diabetic drugs. Communicated by Ramaswamy H. Sarma

Studies of phytochemical constituents by UPLC-QTOF-MS/MS of black hulless barley bran and its antioxidation and α-glucosidase inhibition effect

Anthocyanidins and flavonoids are important components in plant. In present study, the anthocyanidins and flavonoids in black hulless barley bran were identified by operating UPLC-QTOF-MS/MS. Among them, chrysoeriol 7-O-glucouronid, luteolin 7-O-glucouronid, chrysoeriol, and luteolin were quantified by using UPLC. Additionally, the total phenolic content (TPC), total flavonoids content (TFC) and total anthocyanin content (TAC) were determined. Furthermore, the antioxidant activity (via ferric reducing, DPPH and ABTS method) and α-glucosidase inhibition effect were estimated. From the results, fifty-one constituents comprised 19 anthocyanidins and 32 flavonoids were detected in hulless barley bran fractions. Wherein compounds 1 and 9–19 (belong to anthocyanidins), and 21, 25–32, 35–42, 44–50 (belong to flavonoids) were first identified in hulless barley. The contents of chrysoeriol 7-O-glucouronid luteolin 7-O-glucouronid, chrysoeriol and luteolin were higher in E80% than that of in E40%, but were not detected in E20%. Another, the TAC exhibited the trend of E40% > E80% > E20%, and the TPC and TFC showed same trend of E40% > E20% > E80%. The higher TPC and TFC showed stronger antioxidant activity. However, no significant correlation between TAC, TPC, TFC and α-glucosidase inhibitory activity was observed. These results provided the anthocyanidins and flavonoids information, antioxidant value and α-glucosidase inhibition potential, which could provide reference in the development of black hulless barley bran.

Phomopamide A, a cyclic pentadepsipeptide with α-glucosidase inhibition activity from the endophytic fungus Diaporthe sp.

An undescribed cytotoxic cyclopeptide named phomopamide A (1) was isolated from Diaporthe sp., which is an endophytic fungus from Artemisia argyi. Phomopamide A (1) featured an pentadepsipeptide skeleton and composed of two Phe, one Val, one Leu, and one 2-hydroxyoctanoic acid units. The structure of this new compound was fully characterised on the basis of extensive spectroscopic analysis. Moreover, phomopamide A was evaluated for in vitro cyctotoxic and α-glucosidase inhibitory activity. As a result, phomopaminde A exhibited no cytotoxic activity against four tumour cell lines, while it showed a potent α-glucosidase inhibition effect with IC50 value of 62.35 µM.