Porcine pancreatic α-amylase inhibitors from <Emphasis Type="Italic">Euonymus laxiflorus</Emphasis> Champ.

Twenty-six samples of indigenous medicinal plants were collected in Dak Lak Province of Vietnam and evaluated for α-amylase inhibitory activity. Of these samples, trunk bark extract from Euonymus laxiflorus Champ. (ELC extract) showed the greatest α-amylase inhibitory activity with the smallest 50 % inhibitory concentration (IC₅₀) of 6.6 ± 0.6 µg/mL against porcine pancreatic α-amylase. This extract possessed strong inhibitory activity against human saliva α-amylase and slightly lower activity against Bacillus subtilis α-amylase, with IC₅₀ values of 4.2 ± 0.2 and 27.8 ± 1.8 µg/mL, respectively. ELC extract was found to be strongly thermostable, retaining 72–100 % relative activity even after heating at 100 °C for 5 min to 2 h. This extract was also stable at various pH values. These results suggest that ELC extract may be a good candidate for treatment of non-insulin-dependent diabetes mellitus (NIDDM) and obesity.     

Isolation of polyphenol compounds from olive waste and inhibition of their derivatives for α-glucosidase and α-amylase

Abstract

Olive waste was used as a sustainable resource because it contained a variety of valuable compounds. The polyphenols active fraction from enrichment by microporous resin and extraction with ethyl acetate were analysed by different chromatographic methods. A total of 14 polyphenolic compounds were isolated and identified by structure elucidation. Based on the above obtained compounds, tyrosol was selected as a characteristic polyphenol and participated in transesterification reaction to synthesise β-ketoester using Yb(OTf)₃. Then the Biginelli reaction with benzaldehyde, urea and ketoester (1:1.2:1.2) was performed at 90?°C for 3.0?h under the acidic condition. In addition, the β-ketoester prepared using tyrosol with benzyl had a greater inhibitory effect on α-glucosidase and α-amylase, and the inhibition of enzyme activity for 3, 4-dihydropyrimidinone derivatives prepared using abovementioned β-ketoester was improved significantly. Meanwhile, fluorine-containing dihydropyrimidinone derivatives were considerable inhibitors for both enzymes.     

Isolation and characterization of four novel β-Sitosteryl esters from Salvadora persica Linn.

Salvadora persica is virtuous to have a variety of phytoconstituents responsible for many biological activities some of them identified particularly while some are still to be acknowledged. A number of steroidal, glycosidic, terpenoids, saponins and functional esters are reported till date. The present study deals with extraction, isolation, and characterisation of four novel steroidal esters by systematic cold extraction of S. persica. The extracted phytoconstituents were characterised by sophisticated spectral UV, IR, NMR and MS, techniques. The reported four new β-Sitosteryl esters SP-2, 3, 5 and 6 were extracted and reported for the first time.     

Isolation and identification of nondestructive desulfurization bacterium

A nondestructive desulfurization microorganism has been isolated. The metabolism product analyses show that the strain can be a kind of biocatalyst to oxidize dibenzothiophene (DBT) into 2-hydroxydiphenyl (HBP), therefore the sulfur in DBT is removed selectively. The 16SrRNA information, cell wall analysis, physical, biochemical properties and morphological properties suggest that the isolated strain is Rhodococcus erythropolis. The strain can grow in the basal salts medium (BSM) that DBT concentration is no more than 10 mmol/L, and the optimal DBT concentration for growth is 1 mmol/L, however, the optimal DBT concentration for desulfurization is 0.5 mmol/L. The further research shows that the strain can also desulfur some other or-ganosulfur-containing compounds such as thianaphthene, phenyl sulfide and 4,6-dimethyldiben-zothiophene (4,6-DMDBT).     

Validation of the AmpC β-lactamase binding site and identification of inhibitors with novel scaffolds

AmpC β-lactamase confers resistance to β-lactam antibiotics in multiple Gram-negative bacteria. Therefore, identification of non-β-lactam compounds that inhibit the enzyme is considered crucial to the development of novel antibacterial therapies. Given the highly solvent-exposed active site, it is important to study the induced-fit movements and water-mediated interactions to improve docking accuracy and virtual screening enrichments in structure-based design of new AmpC inhibitors. Here, we tested multiple models of the AmpC binding site to investigate the importance of conserved water molecules and binding site plasticity on molecular docking. The results indicate that at least one conserved water molecule greatly improves the binding pose predictions and virtual screening enrichments of known noncovalent AmpC inhibitors. The best model was tested prospectively in the virtual screening of about 6 million commercially available compounds. Sixty-one chemically diverse top-scoring compounds were experimentally tested, which led to the identification of seven previously unknown inhibitors. These findings validate the essential features of the AmpC binding site for molecular recognition and are useful for further optimization of identified inhibitors.     

Isolation and Identification of α-Glucosidase and Protein Glycation Inhibitors from Stereospermum colais

Stereospermum colais (family Bignoniaceae) is a well-known pharmacologically potent medicinal plant reported in traditional systems of medicine. Phytochemical investigation of the roots of S. colais resulted in the isolation of seven compounds, and the metabolites were screened for its α-glucosidase enzyme inhibition and anti-glycation property. The compounds identified were β-sitosterol (1), 2-(4′-hydroxyphenyl) ethyl undecanoate (2), 2-(4′-hydroxyphenyl)ethyl pentadecanoate (3), 5α-ergosta-7,22-dien-3β-ol (4), ursolic acid (5), lapachol (6), and pinoresinol (7). Ursolic acid, lapachol, and pinoresinol possessed IC₅₀ values of 119.01, 130.29, and 125.62 nM, respectively, compared to standard ascorbic acid with an IC₅₀ value of 201.01 nM. The other compounds failed to show the activity. Results of the current study showcased the possible exploration of this medicinal plant for the treatment of type 2 diabetes in line with the development of phytopharmaceutical industry.     

Synthesis and Isolation of α-Oxo Sulfines

The synthesis of several α-oxo sulfines is discribed. Various α-oxo sulfines can be isolated as such. The Diels-Alder reaction of these sulfines with 1,3-dienes can be catalyzed by Lewis acids.     

Rapid screening and identification of α-glucosidase inhibitors from mulberry leaves using enzyme-immobilized magnetic beads coupled with HPLC/MS and NMR

α-Glucosidase plays important roles in the digestion and absorption of carbohydrates in the small intestine. The inhibition of α-glucosidase is regarded as a potential way to treat diabetes. We established an approach to screening α-glucosidase inhibitors from medicinal plants using enzyme-coated magnetic bead. Using 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide and N-hydroxysuccinimide as reaction reagents, α-glucosidase was immobilized on the magnetic beads by covalent linkage. The conjugation of α-glucosidase to the magnetic beads was characterized using scanning electron microscope and X-ray diffractometer. The proposed approach was applied in fishing potential α-glucosidase inhibitors from extract of Morus alba, a Chinese medicinal plant. The structures of potential active compounds were identified via liquid chromatography-mass spectrometry and nuclear magnetic resonance. The results demonstrated that two flavonoids (isoquercitrin and astragalin) could bind to α-glucosidase, which was confirmed via conventional α-glucosidase inhibitory assay. Our findings suggested that enzyme-coated magnetic beads may be suitable for discovering active compounds from medicinal plants.     

Copolymers from α-Pinene. 2. Cationic Copolymerization of Styrene and α-Pinene

A study of the copolymerization of α-pinene and styrene has been carried out at 10°C using anhydrous AlCl₃ as the initiator. It is found that styrene forms copolymer with α-pinene at all mono-meric ratios. A copolymer of 2320–3080 molecular weight is obtained. The softening range of the copolymer is 82 to 85°C. The copolymers are of commercial value.     

Design and synthesis of novel α-aminoamides derivatives as Nav1.7 inhibitors for antinociception

Three novel series of α-aminoamides derivatives were designed and synthesized based on ralfinamide,and their Nav1.7 inhibitory activities were evaluated using manual patch clamp electrophysiology. Active compounds inhibited Nav1.7 with half maximal inhibitory concentration(IC50) values ranging from2.9 μmol/L to 21.4 μmol/L. Among them, the most potent compound 19h exhibited about 12-fold potency better than ralfinamide. The investigation of their structure-activity relationship gives a strategy ...     

Synthesis characterization and evaluation of novel triazole based analogs as a acetylcholinesterase and α-glucosidase inhibitors

A series of novel triazole analogs (10a-k) bearing piperidine were synthesized in an aprotic solvent on the most effective pharmacophore with acetylcholinesterase (AChE) and α-glucosidase inhibitory activity. Triazole analogs (10a-k) were obtained in excellent yields (75–90 %) and characterized by EI-MS, IR, ¹³C NMR and ¹H NMR. The newly synthesized triazole analogs (10a-k) showed potent AChE inhibitory activity in the range of K_i = 0.0155 ± 1.25 µM to 0.557 ± 0.50 µM, IC₅₀ = 0.031 ± 0.85 to 0.537 ± 0.76 µM than Eserine (0.04 ± 0.001 µM) having strong electron-withdrawing fluorine group on the pyridine ring was recorded as a most potent inhibitor of AChE while (%) inhibition against α-glucosidase was ranging between 52.36 ± 1.67 to 85.35 ± 1.39. The kinetic study predicted that triazole analogs (10a-k) followed the un-competitive and mixed type of inhibition against AChE. In silico molecular docking was performed at the active site of the AChE co-crystal structure (PDB ID:1NEN). The results of molecular docking corelate will with the experimental findings.     

Chemical composition and α-amylase inhibitory activity of the essential oil from Sabina chinensis cv. Kaizuca leaves

Sabina chinensis cv. Kaizuca (SCK) is a variant of S. chinensis L. The essential oil from its leaves exhibited α-amylase inhibitory activity in vitro and the IC₅₀ value was 187.08 ± 0.56 μg/mL. Nineteen compounds were identified from this essential oil by gas chromatography–mass spectrometry (GC-MS) analysis. The major compounds identified were bornyl acetate (42.6%), elemol (20.5%), β-myrcene (13.7%) and β-linalool (4.0%). In order to study the reason of the α-amylase inhibitory activity of this essential oil, the identified compounds were docked with α-amylase by molecular docking individually. Among these compounds, γ-eudesmol exhibited the lowest binding energy (?6.73 kcal/mol), followed by α-copaen-11-ol (?6.66 kcal/mol), cubedol (?6.39 kcal/mol) and α-acorenol (?6.12 kcal/mol). The results indicated that these compounds were the active ingredients responsible for the α-amylase inhibitory activity of essential oil from SCK.     

Isolation and Characterization of a Bioactive Polysaccharide from Panax Quinquefolium L.

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Synthesis and α-amylase inhibitory activity of glucose-deoxynojirimycin conjugates

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.     

Isolation, Purification, and Properties of α-Amylase from Bacillus subtilis-7A

Cultivation ofBacillus subtilis-7A on waste from alcohol production yielded an active extracellular enzyme -amylase with MW 75 kDa. The enzyme was isolated from the culture medium by 60% saturated ammonium sulfate and purified until homogeneous by gel filtration on Sephadex G-100 and ion-exchange chromatography on DEAE-cellulose. The optimum temperatures for the complex and purified enzyme are 30 and 50°C, respectively. The optimum activity for both preparations occurred at pH 6.5. The substrate specificity of the isolated preparations was studied.     

The Non-degradative Isolation of α1-Acid Glycoprotein from Normal and Rheumatoid Plasma1

Abstract

We have developed a method for the purification of α₁-acid glycoprotein (AGP) using procedures unlikely to damage the glycoprotein structure. This was utilised to isolate AGP from samples of normal and rheumatoid plasma. The effectiveness of the purification procedure was examined by enzymatically deglycosylating each sample of AGP, separating the released oligosaccharides by chromatography on a pellicular high pH anion-exchange (HPAE) resin at pH 13 and detecting by a pulsed electrochemical (PED) method. The analytical profile for normal AGP was consistent with those previously reported thus indicating that the purification procedure did not denature the oligosaccharide chains of AGP; there was a noticeable difference between AGP in normal and rheumatoid plasma.     

Structure-based approach for identification of novel phenylboronic acids as serine-β-lactamase inhibitors

β-Lactamases are bacterial enzymes conferring resistance to β-lactam antibiotics in clinically-relevant pathogens, and represent relevant drug targets. Recently, the identification of new boronic acids (i.e. RPX7009) paved the way to the clinical application of these molecules as potential drugs. Here, we screened in silico a library of ~1400 boronic acids as potential AmpC β-lactamase inhibitors. Six of the most promising candidates were evaluated in biochemical assays leading to the identification of potent inhibitors of clinically-relevant β-lactamases like AmpC, KPC-2 and CTX-M-15. One of the selected compounds showed nanomolar K _i value with the clinically-relevant KPC-2 carbapenemase, while another one exhibited broad spectrum inhibition, being also active on Enterobacter AmpC and the OXA-48 class D carbapenemase.     

Isolation and Characterization of Antimicrobial Polypeptide from Loach

A novel antimicrobial polypeptide was isoated and characterized from loach,misgurnus anguillicaudatus.The polypeptide,named MAPP,is a single-chain polypeptide with Mw adout 9,800 Dalton and pI about 4.78:the N-tag of MAPP was CFGWN.MAPP showed good inhibition against various bacteria including Bacillus subtilis.Escherichia coli and Staphylococcus aureus.MAPP could be used as a lead compound in antibiotics drug discovery.     

Isolation and Characterization of C-phycocyanin from Spirulina Platensis

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