Displaying publications 1 - 20 of 56 in total

Abstract:
Sort:
  1. Zawawi NK, Taha M, Ahmat N, Wadood A, Ismail NH, Rahim F, et al.
    Bioorg. Chem., 2016 Feb;64:29-36.
    PMID: 26637946 DOI: 10.1016/j.bioorg.2015.11.006
    Newly synthesized benzimidazole hydrazone derivatives 1-26 were evaluated for their α-glucosidase inhibitory activity. Compounds 1-26 exhibited varying degrees of yeast α-glucosidase inhibitory activity with IC50 values between 8.40 ± 0.76 and 179.71 ± 1.11 μM when compared with standard acarbose. In this assay, seven compounds that showed highest inhibitory effects than the rest of benzimidazole series were identified. All the synthesized compounds were characterized by different spectroscopic methods adequately. We further evaluated the interaction of the active compounds with enzyme with the help of docking studies.
    Matched MeSH terms: alpha-Glucosidases/chemistry*
  2. Al-Salahi R, Ahmad R, Anouar E, Iwana Nor Azman NI, Marzouk M, Abuelizz HA
    Future Med Chem, 2018 08 01;10(16):1889-1905.
    PMID: 29882426 DOI: 10.4155/fmc-2018-0141
    AIM: Using a simple modification on a previously reported synthetic route, 3-benzyl(phenethyl)-2-thioxobenzo[g]quinazolin-4(3H)-ones (1 and 2) were synthesized with high yields. Further transformation of 1 and 2 produced derivatives 3-26, which were structurally characterized based on NMR and MS data, and their in vitro α-glucosidase inhibitory activity was evaluated using Baker's yeast α-glucosidase enzyme.

    RESULTS: Compounds 2, 4, 8, 12 and 20 exhibited the highest activity (IC50 = 69.20, 59.60, 49.40, 50.20 and 83.20 μM, respectively) compared with the standard acarbose (IC50 = 143.54 μM).

    CONCLUSION: A new class of potent α-glucosidase inhibitors was identified, and the molecular docking predicted plausible binding interaction of the targets in the binding pocket of α-glucosidase and rationalized the structure-activity relationship (SARs) of the target compounds.

    Matched MeSH terms: alpha-Glucosidases/metabolism*
  3. Saleem H, Zengin G, Ahmad I, Lee JTB, Htar TT, Mahomoodally FM, et al.
    J Pharm Biomed Anal, 2019 Jun 05;170:132-138.
    PMID: 30921647 DOI: 10.1016/j.jpba.2019.03.027
    The current research work was conducted in order to probe into the biochemical and toxicological characterisation of methanol and dichloromethane (DCM) extracts of Bougainvillea glabra (Choisy.) aerial parts. Biological fingerprints were assessed for in vitro antioxidant, key enzyme inhibitory and cytotoxicity potential. Total bioactive contents were determined spectrophotometrically and the secondary metabolite components of methanol extract was assessed by UHPLC mass spectrometric analysis. The antioxidant capabilities were evaluated via six different in vitro antioxidant assays namely DPPH, ABTS (free radical scavenging), FRAP, CUPRAC (reducing antioxidant power), phosphomolybdenum (total antioxidant capacity) and ferrous chelating activity. Inhibition potential against key enzymes urease, α-glucosidase and cholinesterases were also determined. Methanol extract exhibited higher phenolic (24.01 mg GAE/g extract) as well as flavonoid (41.51 mg QE/g extract) contents. Phytochemical profiling of methanol extract identified a total of twenty secondary metabolites and the major compounds belonged to flavonoids, phenolics and alkaloid derivatives. The findings of antioxidant assays revealed the methanol extract to exhibit stronger antioxidant (except phosphomolybdenum) activities. Similarly, the methanol extract showed highest butyrylcholinesterase and urease inhibition. The DCM extract was most active for phosphomolybdenum and α-glucosidase inhibition assays. Moreover, both extracts exhibited significant cytotoxic potential against five (MCF-7, MDA-MB-231, CaSki, DU-145, and SW-480) human carcinoma cell lines with half maximal inhibitory concentration values of 22.09 to 257.2 μg/mL. Results from the present study highlighted the potential of B. glabra aerial extracts to be further explored in an endeavour to discover novel phytotherapeutics as well as functional ingredients.
    Matched MeSH terms: alpha-Glucosidases/chemistry
  4. Saleem F, Mehmood R, Mehar S, Khan MTJ, Khan ZU, Ashraf M, et al.
    Antioxidants (Basel), 2019 Jul 19;8(7).
    PMID: 31331076 DOI: 10.3390/antiox8070231
    Members of genus Pteris have their established role in the traditional herbal medicine system. In the pursuit to identify its biologically active constituents, the specie Pteris cretica L. (P. cretica) was selected for the bioassay-guided isolation. Two new maleates (F9 and CB18) were identified from the chloroform extract and the structures of the isolates were elucidated through their spectroscopic data. The putative targets, that potentially interact with both of these isolates, were identified through reverse docking by using in silico tools PharmMapper and ReverseScreen3D. On the basis of reverse docking results, both isolates were screened for their antioxidant, acetylcholinesterase (AChE) inhibition, α-glucosidase (GluE) inhibition and antibacterial activities. Both isolates depicted moderate potential for the selected activities. Furthermore, docking studies of both isolates were also studied to investigate the binding mode with respective targets followed by molecular dynamics simulations and binding free energies. Thereby, the current study embodies the poly-pharmacological potential of P. cretica.
    Matched MeSH terms: alpha-Glucosidases
  5. Rafique R, Khan KM, Arshia, Kanwal, Chigurupati S, Wadood A, et al.
    Bioorg. Chem., 2019 Aug 23.
    PMID: 31451297 DOI: 10.1016/j.bioorg.2019.103195
    The current study describes the discovery of novel inhibitors of α-glucosidase and α-amylase enzymes. For that purpose, new hybrid analogs of N-hydrazinecarbothioamide substituted indazoles 4-18 were synthesized and fully characterized by EI-MS, FAB-MS, HRFAB-MS, 1H-, and 13C NMR spectroscopic techniques. Stereochemistry of the imine double bond was established by NOESY measurements. All derivatives 4-18 with their intermediates 1-3, were evaluated for in vitro α-glucosidase and α-amylase enzyme inhibition. It is worth mentioning that all synthetic compounds showed good inhibition potential in the range of 1.54 ± 0.02-4.89 ± 0.02 µM for α-glucosidase and for α-amylase 1.42 ± 0.04-4.5 ± 0.18 µM in comparison with the standard acarbose (IC50 value of 1.36 ± 0.01 µM). In silico studies were carried out to rationalize the mode of binding interaction of ligands with the active site of enzymes. Moreover, enzyme inhibitory kinetic characterization was also performed to understand the mechanism of enzyme inhibition.
    Matched MeSH terms: alpha-Glucosidases
  6. Abuelizz HA, Anouar EH, Ahmad R, Azman NIIN, Marzouk M, Al-Salahi R
    PLoS ONE, 2019;14(8):e0220379.
    PMID: 31412050 DOI: 10.1371/journal.pone.0220379
    Previously, we synthesized triazoloquinazolines 1-14 and characterized their structure. In this study, we aimed to evaluate the in vitro activity of the targets 1-14 as α-glucosidase inhibitors using α-glucosidase enzyme from Saccharomyces cerevisiae type 1. Among the tested compounds, triazoloquinazolines 14, 8, 4, 5, and 3 showed the highest inhibitory activity (IC50 = 12.70 ± 1.87, 28.54 ± 1.22, 45.65 ± 4.28, 72.28 ± 4.67, and 83.87 ± 5.12 μM, respectively) in relation to that of acarbose (IC50 = 143.54 ± 2.08 μM) as a reference drug. Triazoloquinazolines were identified herein as a new class of potent α-glucosidase inhibitors. Molecular docking results envisaged the plausible binding interaction between the target triazoloquinazolines and α-glucosidase enzyme and indicated considerable interaction with the active site residues.
    Matched MeSH terms: alpha-Glucosidases
  7. Wahab NA, Abdullah N, Aminudin N
    Biomed Res Int, 2014;2014:131607.
    PMID: 25243114 DOI: 10.1155/2014/131607
    Pleurotus pulmonarius has been reported to have a potent remedial effect on diabetic property and considered to be an alternative for type 2 diabetes mellitus treatment. This study aimed to investigate the antidiabetic properties of ammonium sulphate precipitated protein fractions from P. pulmonarius basidiocarps. Preliminary results demonstrated that 30% (NH4)2SO4 precipitated fraction (F30) inhibited Saccharomyces cerevisiae α-glucosidase activity (24.18%), and 100% (NH4)2SO4 precipitated fraction (F100) inhibited porcine pancreatic α-amylase activity (41.80%). Following RP-HPLC purification, peak 3 from F30 fraction demonstrated inhibition towards α-glucosidase at the same time with meagre inhibition towards α-amylase activity. Characterisation of proteins using MALDI-TOF/TOF MS demonstrated the presence of four different proteins, which could be implicated in the regulation of blood glucose level via various mechanisms. Therefore, this study revealed the presence of four antidiabetic-related proteins which are profilin-like protein, glyceraldehyde-3-phosphate dehydrogenase-like protein, trehalose phosphorylase-like (TP-like) protein, and catalase-like protein. Hence, P. pulmonarius basidiocarps have high potential in lowering blood glucose level, reducing insulin resistance and vascular complications.
    Matched MeSH terms: alpha-Glucosidases/metabolism
  8. Yusoff NA, Ahmad M, Al-Hindi B, Widyawati T, Yam MF, Mahmud R, et al.
    Nutrients, 2015 Aug;7(8):7012-26.
    PMID: 26308046 DOI: 10.3390/nu7085320
    Nypa fruticans Wurmb. vinegar, commonly known as nipa palm vinegar (NPV) has been used as a folklore medicine among the Malay community to treat diabetes. Early work has shown that aqueous extract (AE) of NPV exerts a potent antihyperglycemic effect. Thus, this study is conducted to evaluate the effect of AE on postprandial hyperglycemia in an attempt to understand its mechanism of antidiabetic action. AE were tested via in vitro intestinal glucose absorption, in vivo carbohydrate tolerance tests and spectrophotometric enzyme inhibition assays. One mg/mL of AE showed a comparable outcome to the use of phloridzin (1 mM) in vitro as it delayed glucose absorption through isolated rat jejunum more effectively than acarbose (1 mg/mL). Further in vivo confirmatory tests showed AE (500 mg/kg) to cause a significant suppression in postprandial hyperglycemia 30 min following respective glucose (2 g/kg), sucrose (4 g/kg) and starch (3 g/kg) loadings in normal rats, compared to the control group. Conversely, in spectrophotometric enzymatic assays, AE showed rather a weak inhibitory activity against both α-glucosidase and α-amylase when compared with acarbose. The findings suggested that NPV exerts its anti-diabetic effect by delaying carbohydrate absorption from the small intestine through selective inhibition of intestinal glucose transporters, therefore suppressing postprandial hyperglycemia.
    Matched MeSH terms: alpha-Glucosidases/metabolism
  9. Sivasothy Y, Loo KY, Leong KH, Litaudon M, Awang K
    Phytochemistry, 2016 Feb;122:265-269.
    PMID: 26712615 DOI: 10.1016/j.phytochem.2015.12.007
    A dimeric acylphenol and a potent α-glucosidase inhibitor, giganteone D (IC50 5.05μM), was isolated and characterized from the bark of Myristica cinnamomea King. The bark also yielded an acylphenol with an unprecedented skeleton for which the name cinnamomeone A (IC50 358.80μM) was proposed. Their structures were established by means of NMR and MS spectrometric analyses. The Lineweaver-Burk plot of giganteone D indicated that it was a mixed-type inhibitor. This is the first report on the α-glucosidase inhibiting potential of acylphenols.
    Matched MeSH terms: alpha-Glucosidases/drug effects*
  10. Loo KY, Leong KH, Sivasothy Y, Ibrahim H, Awang K
    Chem. Biodivers., 2019 Jun;16(6):e1900032.
    PMID: 30957403 DOI: 10.1002/cbdv.201900032
    The inhibition of carbohydrate-hydrolyzing enzymes in human digestive organs is crucial in controlling blood sugar levels, which is important in treating type 2 diabetes. In the current study, pahangensin A (1), a bis-labdanic diterpene characterized previously in the rhizomes of Alpinia pahangensis Ridl., was identified as an active dual inhibitor for α-amylase (IC50 =114.80 μm) and α-glucosidase (IC50 =153.87 μm). This is the first report on the dual α-amylase and α-glucosidase inhibitory activities of a bis-labdanic diterpene. The Lineweaver-Burk plots of compound 1 indicate that it is a mixed-type inhibitor with regard to both enzymes. Based on molecular docking studies, compound 1 docked in a non-active site of both enzymes. The dual inhibitory activity of compound 1 makes it a suitable natural alternative in the treatment of type 2 diabetes.
    Matched MeSH terms: alpha-Glucosidases/metabolism*; alpha-Glucosidases/chemistry
  11. Lee, S.Y., Mediani, A., Nur Ashikin, A.H., Abas, F., Azliana, A.B.S.
    MyJurnal
    The study was aimed to determine the antioxidant and α-glucosidase inhibition activities of
    the stem and leaf of five different traditional medicinal plants. The studied plants exhibited
    varied antioxidant and α-glucosidase inhibition activities. The antioxidant activities of the
    plants were determined through their free radical scavenging capabilities using DPPH assay.
    The most potent antioxidant activity was demonstrated by Neptunia oleracea with an IC50 of
    35.45 and 29.72 μg/mL for leaf and stem, respectively. For α-glucosidase inhibition activity,
    Neptunia oleracea exhibited potential α-glucosidase inhibition activity with IC50 value of
    19.09 and 19.74 μg/mL for leaf and stem, respectively. The highest total phenolic content
    (TPC) was also marked in Neptunia oleracea leaf and stem with value of 40.88 and 21.21 mg
    GAE/g dry weight, respectively. The results also showed that Strobilanthes crispus collected
    from two different locations possessed different levels of phenolic content, antioxidant and
    α-glucosidase inhibition activities. The study revealed that phenolic compounds could be the
    main contributors to the antioxidant and α-glucosidase inhibition activities with R values of 78.9
    and 67.4%, respectively. In addition, antioxidant and α-glucosidase were positively correlated
    (R = 81.9%). Neptunia oleracea could be suggested as a potential natural source of antioxidant
    and antidiabetic compounds that can be used for the prevention or treatment of diabetes.
    Matched MeSH terms: alpha-Glucosidases
  12. Khan KM, Rahim F, Wadood A, Kosar N, Taha M, Lalani S, et al.
    Eur J Med Chem, 2014 Jun 23;81:245-52.
    PMID: 24844449 DOI: 10.1016/j.ejmech.2014.05.010
    In our effort directed toward the discovery of new anti-diabetic agent for the treatment of diabetes, a library of biscoumarin derivative 1-18 was synthesized and evaluated for α-glucosidase inhibitory potential. All eighteen (18) compounds displayed assorted α-glucosidase activity with IC50 values 16.5-385.9 μM, if compared with the standard acarbose (IC50 = 906 ± 6.387 μM). In addition, molecular docking studies were carried out to explore the binding interactions of biscoumarin derivatives with the enzyme. This study has identified a new class of potent α-glucosidase inhibitors.
    Matched MeSH terms: alpha-Glucosidases/metabolism*
  13. Taha M, Ismail NH, Lalani S, Fatmi MQ, Atia-Tul-Wahab, Siddiqui S, et al.
    Eur J Med Chem, 2015 Mar 6;92:387-400.
    PMID: 25585009 DOI: 10.1016/j.ejmech.2015.01.009
    In an effort to design and synthesize a new class of α-glucosidase inhibitor, we synthesized benzothiazole hybrid having benzohydrazide moiety (5). Compound 5 was reacted with various substituted aryl aldehyde to generate a small library of compounds 6-35. Synthesis of compounds was confirmed by the spectral information. These compounds were screened for their α-glucosidase activity. They showed a varying degree of α-glucosidase inhibition with IC50 values ranging between 5.31 and 53.34 μM. Compounds 6, 7, 9-16, 19, 21-30, 32-35 showed superior activity as compared to standard acarbose (IC50 = 906 ± 6.3 μM). This has identified a new class of α-glucosidase inhibitors. The predicted physico-chemical properties indicated the drug appropriateness for most of these compounds, as they obey Lipinski's rule of five (RO5). A hybrid B3LYP density functional theory (DFT) was employed for energy, minimization of 3D structures for all synthetic compounds using 6-311 + G(d,p) basis sets followed by molecular docking to explore their interactions with human intestinal C- and N-terminal domains of α-glucosidase. All compounds bind to the prospective allosteric site of the C- terminal domain, and consequently, may be considered as mixed inhibitors. It was hypothesized that both the dipole moment and H-bond interactions govern the biological activation of these compounds.
    Matched MeSH terms: alpha-Glucosidases/metabolism*
  14. Alasmary FAS, Alnahdi FS, Ben Bacha A, El-Araby AM, Moubayed N, Alafeefy AM, et al.
    J Enzyme Inhib Med Chem, 2017 Dec;32(1):1143-1151.
    PMID: 28856929 DOI: 10.1080/14756366.2017.1363743
    Elevated blood glucose and increased activities of secreted phospholipase A2 (sPLA2) are strongly linked to coronary heart disease. In this report, our goal was to develop small heterocyclic compound that inhibit sPLA2. The title compounds were also tested against α-glucosidase and α-amylase. This array of enzymes was selected due to their implication in blood glucose regulation and diabetic cardiovascular complications. Therefore, two distinct series of quinoxalinone derivatives were synthesised; 3-[N'-(substituted-benzylidene)-hydrazino]-1H-quinoxalin-2-ones 3a-f and 1-(substituted-phenyl)-5H-[1,2,4]triazolo[4,3-a]quinoxalin-4-ones 4a-f. Four compounds showed promising enzyme inhibitory effect, compounds 3f and 4b-d potently inhibited the catalytic activities of all of the studied proinflammatory sPLA2. Compound 3e inhibited α-glucosidase (IC50 = 9.99 ± 0.18 µM); which is comparable to quercetin (IC50 = 9.93 ± 0.66 µM), a known inhibitor of this enzyme. Unfortunately, all compounds showed weak activity against α-amylase (IC50 > 200 µM). Structure-based molecular modelling tools were utilised to rationalise the SAR compared to co-crystal structures with sPLA2-GX as well as α-glucosidase. This report introduces novel compounds with dual activities on biochemically unrelated enzymes mutually involved in diabetes and its complications.
    Matched MeSH terms: alpha-Glucosidases/metabolism*
  15. Wan-Nadilah WA, Akhtar MT, Shaari K, Khatib A, Hamid AA, Hamid M
    BMC Complement Altern Med, 2019 Sep 05;19(1):245.
    PMID: 31488132 DOI: 10.1186/s12906-019-2655-9
    BACKGROUND: Cosmos caudatus is an annual plant known for its medicinal value in treating several health conditions, such as high blood pressure, arthritis, and diabetes mellitus. The α-glucosidase inhibitory activity and total phenolic content of the leaf aqueous ethanolic extracts of the plant at different growth stages (6, 8. 10, 12 and 14 weeks) were determined in an effort to ascertain the best time to harvest the plant for maximum medicinal quality with respect to its glucose-lowering effects.

    METHODS: The aqueous ethanolic leaf extracts of C. caudatus were characterized by NMR and LC-MS/MS. The total phenolic content and α-glucosidase inhibitory activity were evaluated by the Folin-Ciocalteu method and α-glucosidase inhibitory assay, respectively. The statistical significance of the results was evaluated using one-way ANOVA with Duncan's post hoc test, and correlation among the different activities was performed by Pearson's correlation test. NMR spectroscopy along with multivariate data analysis was used to identify the metabolites correlated with total phenolic content and α-glucosidase inhibitory activity of the C. caudatus leaf extracts.

    RESULTS: It was found that the α-glucosidase inhibitory activity and total phenolic content of the optimized ethanol:water (80:20) leaf extract of the plant increased significantly as the plant matured, reaching a maximum at the 10th week. The IC50 value for α-glucosidase inhibitory activity (39.18 μg mL- 1) at the 10th week showed greater potency than the positive standard, quercetin (110.50 μg mL- 1). Through an 1H NMR-based metabolomics approach, the 10-week-old samples were shown to be correlated with a high total phenolic content and α-glucosidase inhibitory activity. From the partial least squares biplot, rutin and flavonoid glycosides, consisting of quercetin 3-O-arabinofuranoside, quercetin 3-O-rhamnoside, quercetin 3-O-glucoside, and quercetin 3-O-xyloside, were identified as the major bioactive metabolites. The metabolites were identified by NMR spectroscopy (J-resolve, HSQC and HMBC experiments) and further supported by dereplication via LC-MS/MS.

    CONCLUSION: For high phytomedicinal quality, the 10th week is recommended as the best time to harvest C. caudatus leaves with respect to its glucose lowering potential.

    Matched MeSH terms: alpha-Glucosidases
  16. Iftikhar M, Shahnawaz, Saleem M, Riaz N, Aziz-Ur-Rehman, Ahmed I, et al.
    PMID: 31544284 DOI: 10.1002/ardp.201900095
    A series of new N-aryl/aralkyl derivatives of 2-methyl-2-{5-(4-chlorophenyl)-1,3,4-oxadiazole-2ylthiol}acetamide were synthesized by successive conversions of 4-chlorobenzoic acid (a) into ethyl 4-chlorobenzoate (1), 4-chlorobenzoylhydrazide (2) and 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-thiol (3), respectively. The required array of compounds (6a-n) was obtained by the reaction of 1,3,4-oxadiazole (3) with various electrophiles (5a-n) in the presence of DMF (N,N-dimethylformamide) and sodium hydroxide at room temperature. The structural determination of these compounds was done by infrared, 1 H-NMR (nuclear magnetic resonance), 13 C-NMR, electron ionization mass spectrometry, and high-resolution electron ionization mass spectrometry analyses. All compounds were evaluated for their α-glucosidase inhibitory potential. Compounds 6a, 6c-e, 6g, and 6i were found to be promising inhibitors of α-glucosidase with IC50 values of 81.72 ± 1.18, 52.73 ± 1.16, 62.62 ± 1.15, 56.34 ± 1.17, 86.35 ± 1.17, 52.63 ± 1.16 µM, respectively. Molecular modeling and ADME (absorption, distribution, metabolism, excretion) predictions supported the findings. The current synthesized library of compounds was achieved by utilizing very common raw materials in such a way that the synthesized compounds may prove to be promising drug leads.
    Matched MeSH terms: alpha-Glucosidases
  17. Zhu J, Zhang B, Tan C, Huang Q
    Food Funct, 2019 Sep 13.
    PMID: 31517355 DOI: 10.1039/c9fo01333d
    The present study aims to investigate the relationship between in silico experimental data and in vitro inhibitory data of polyphenols against α-glucosidase. The CDOCKER protocol in Discovery Studio was used to dock various polyphenols to the Saccharomyces cerevisiae α-glucosidase crystal structure. -CDOCKER energy values and the energy gap between the highest occupied molecular orbital energy and the lowest unoccupied molecular orbital energy were used to study its consistency with in vitro inhibitory data. The results showed that the correlation trend was trustworthy regardless of the data deviation and low correlation coefficient. Despite slight disagreements with some specific polyphenols, the docking data generally explained the effect of the groups (-OH, glycosyl, galloyl, and caffeoyl). The docking results showed that compound 7, a quercetin derivative, can be recommended as a lead antidiabetic compound, with additional anti-obesity effects. Galloyl and caffeoyl moieties are favorable to develop novel αG inhibitors.
    Matched MeSH terms: alpha-Glucosidases
  18. Arshad T, Khan KM, Rasool N, Salar U, Hussain S, Asghar H, et al.
    Bioorg. Chem., 2017 06;72:21-31.
    PMID: 28346872 DOI: 10.1016/j.bioorg.2017.03.007
    On the basis of previous report on promising α-glucosidase inhibitory activity of 5-bromo-2-aryl benzimidazole derivatives, these derivatives were further screened for urease inhibitory and cytotoxicity activity in order to get more potent and non-cytotoxic potential dual inhibitor for the patients suffering from diabetes as well as peptic ulcer. In this study, all compounds showed varying degree of potency in the range of (IC50=8.15±0.03-354.67±0.19μM) as compared to standard thiourea (IC50=21.25±0.15μM). It is worth mentioning that derivatives 7 (IC50=12.07±0.05μM), 8 (IC50=10.57±0.12μM), 11 (IC50=13.76±0.02μM), 14 (IC50=15.70±0.12μM) and 22 (IC50=8.15±0.03μM) were found to be more potent inhibitors than standard. All compounds were also evaluated for cytotoxicity towards 3T3 mouse fibroblast cell line and found to be completely non-toxic. Previously benzimidazole 1-25 were also showed α-glucosidase inhibitory potential. In silico studies were performed on the lead molecules i.e.2, 7, 8, 11, 14, and 22, in order to rationalize the binding interaction of compounds with the active site of urease enzyme.
    Matched MeSH terms: alpha-Glucosidases/metabolism*
  19. Nawawi HM, Yazid TN, Ismail F, Khalid BA
    Asia Pac J Clin Nutr, 2000 Mar;9(1):41-5.
    PMID: 24394314
    Acarbose inhibits intestinal alpha-glucosidases resulting in diminished and delayed postprandial hyperglycaemia (PPH). Studies on effects of acarbose on postprandial lipaemia (PPL) have been inconclusive. Little is known about the effects of acarbose on PPH and PPL following intake of a polysaccharide diet. We studied 30 type 2 diabetic patients on dietary and/or oral hypoglycaemic agent(s). Thirty patients were recruited for food A (nasi lemak), 28 for food B (mee goreng) and 28 for food C (roti telur), which represent the typical diets of the three main races in Malaysia. Serial blood samples were taken at 15 min before and up to 240 min after each food intake, without acarbose. Subsequently, three doses of 50 mg acarbose were given orally and the same procedure was repeated the following day. There were significantly lower mean increments in plasma glucose levels after compared to before acarbose treatment 30, 45 and 60 min for food A and at 30, 45, 60, 120, 180 and 240 min for food C, but no significant difference was noted for food B. There was a significantly lower mean fasting glucose level after compared with before acarbose treatment following intake of food A and C but not food B. Short-term treatment with acarbose caused significant diminished and delayed PPH response with food A and C but not with food B. Acarbose was more effective in reducing PPH response in polysaccharide foods with a higher and earlier postprandial glucose peak than in those with a lower and lagged peak. There were no significant differences in the mean fasting or postprandial triglyceride levels before and after acarbose treatment, following intake of all three foods for up to 4 hours. Depending on the food absorption pattern, overnight low dose treatment with acarbose leads to diminished fasting and peak plasma glucose levels, and delayed PPH but insignificant reduction in postprandial lipaemia in poorly controlled type 2 diabetics following intake of racially different Malaysian food.
    Matched MeSH terms: alpha-Glucosidases
  20. Taha M, Ismail NH, Imran S, Rokei MQ, Saad SM, Khan KM
    Bioorg. Med. Chem., 2015 Aug 1;23(15):4155-62.
    PMID: 26183542 DOI: 10.1016/j.bmc.2015.06.060
    Oxadiazole derivatives (6-28) having hydrazone linkage, were synthesized through condensation reaction between benzohydrazide 5 with various benzaldehydes. The oxadiazoles derivatives (6-28) were evaluated for their α-glucosidase inhibitory activity. The IC50 values for inhibition activity vary in the range between 2.64 ± 0.05 and 460.14 ± 3.25 μM. The IC50 values were being compared to the standard acarbose (IC50=856.45 ± 5.60 μM) and it was found that compounds 6-9, 12, 13, 16, 18, 20, 22-28 were found to be more active than acarbose, while other compounds showed no activity. Structure-activity relationship (SAR) studies suggest that oxadiazole benzohydrazones (6-28) inhibitory potential is dependent on substitution of the N-benzylidene part. Compound 18 (IC50=2.64 ± 0.05 μM), which has trihydroxy substitution at C-2', C-4', and C-5' on N-benzylidene moiety, recorded the highest inhibition activity that is three-hundred times more active than the standard drug, acarbose (IC50=856.45 ± 5.60 μM). Compound 23 (IC50=34.64 ± 0.35 μM) was found to be the most active among compounds having single hydroxyl substitution. Shifting hydroxyl from C-2' to C-4' (6) and C-3' (7) reduces inhibitory activity significantly. Compounds with chlorine substituent (compounds 16, 28, and 27) showed potent activities but lower as compared to hydroxyl analogs. Substituent like nitro or methyl groups at any position suppresses enzyme inhibition activity. This reveals the important presence of hydroxyl and halo groups to have enzyme inhibitory potential.
    Matched MeSH terms: alpha-Glucosidases
Filters
Contact Us

Please provide feedback to Administrator (tengcl@gmail.com)

External Links