Displaying all 12 publications

Abstract:
Sort:
  1. Nakamoto H, Amaya Y, Komatsu T, Suzuki T, Dohmae N, Nakamura Y, et al.
    Biochem. J., 2018 08 16;475(15):2559-2576.
    PMID: 30045873 DOI: 10.1042/BCJ20180230
    Hsp90 is an ATP-dependent molecular chaperone that assists folding and conformational maturation/maintenance of many proteins. It is a potential cancer drug target because it chaperones oncoproteins. A prokaryotic homolog of Hsp90 (HtpG) is essential for thermo-tolerance in some bacteria and virulence of zoonotic pathogens. To identify a new class of small molecules which target prokaryotic and eukaryotic Hsp90s, we studied the effects of a naturally occurring cyclic sesquiterpene, zerumbone, which inhibits proliferation of a wide variety of tumor cells, on the activity of Hsp90. Zerumbone enhanced the ATPase activity of cyanobacterial Hsp90 (Hsp90SE), yeast Hsp90, and human Hsp90α. It also enhanced the catalytic efficiency of Hsp90SE by greatly increasing kcat Mass analysis showed that zerumbone binds to cysteine side chains of Hsp90SE covalently. Mutational studies identified 3 cysteine residues (one per each domain of Hsp90SE) that are involved in the enhancement, suggesting the presence of allosteric sites in the middle and C-terminal domains of Hsp90SE Treatment of cyanobacterial cells with zerumbone caused them to become very temperature-sensitive, a phenotype reminiscent of cyanobacterial Hsp90 mutants, and also decreased the cellular level of linker polypeptides that are clients for Hsp90SE Zerumbone showed cellular toxicity on cancer-derived mammalian cells by inducing apoptosis. In addition, zerumbone inhibited the binding of Hsp90/Cdc37 to client kinases. Altogether, we conclude that modification of cysteine residues of Hsp90 by zerumbone enhances its ATPase activity and inhibits physiological Hsp90 function. The activation of Hsp90 may provide new strategies to inhibit its chaperone function in cells.
    Matched MeSH terms: Saccharomyces cerevisiae/enzymology*
  2. 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: Saccharomyces cerevisiae/enzymology*
  3. Rahim F, Malik F, Ullah H, Wadood A, Khan F, Javid MT, et al.
    Bioorg Chem, 2015 Jun;60:42-8.
    PMID: 25955493 DOI: 10.1016/j.bioorg.2015.03.005
    Isatin base Schiff bases (1-20) were synthesized, characterized by (1)H NMR and EI/MS and evaluated for α-glucosidase inhibitory potential. Out of these twenty (20) compounds only six analogs showed potent α-glucosidase inhibitory potential with IC50 value ranging in between 2.2±0.25 and 83.5±1.0μM when compared with the standard acarbose (IC50=840±1.73μM). Among the series compound 2 having IC50 value (18.3±0.56μM), 9 (83.5±1.0μM), 11 (3.3±0.25μM), 12 (2.2±0.25μM), 14 (11.8±0.15μM), and 20 (3.0±0.15μM) showed excellent inhibitory potential many fold better than the standard acarbose. The binding interactions of these active analogs were confirmed through molecular docking.
    Matched MeSH terms: Saccharomyces cerevisiae/enzymology
  4. Zawawi NK, Taha M, Ahmat N, Ismail NH, Wadood A, Rahim F
    Bioorg Chem, 2017 02;70:184-191.
    PMID: 28043716 DOI: 10.1016/j.bioorg.2016.12.009
    Thiourea derivatives having benzimidazole 1-17 have been synthesized, characterized by 1H NMR, 13C NMR and EI-MS and evaluated for α-glucosidase inhibition. Identification of potential α-glucosidase inhibitors were done by in vitro screening of 17 thiourea bearing benzimidazole derivatives using Baker's yeast α-glucosidase enzyme. Compounds 1-17 exhibited a varying degree of α-glucosidase inhibitory activity with IC50 values between 35.83±0.66 and 297.99±1.20μM which are more better than the standard acarbose (IC50=774.5±1.94μM). Compound 10 and 14 showed significant inhibitory effects with IC50 value 50.57±0.81 and 35.83±0.66μM, respectively better than the rest of the series. Structure activity relationships were established. Molecular docking studies were performed to understand the binding interaction of the compounds.
    Matched MeSH terms: Saccharomyces cerevisiae/enzymology*
  5. Chen KH, Lee SY, Show PL, Hong SC, Chang YK
    J Chromatogr B Analyt Technol Biomed Life Sci, 2018 Nov 15;1100-1101:65-75.
    PMID: 30292951 DOI: 10.1016/j.jchromb.2018.09.039
    Dye-ligand affinity chromatography in a stirred fluidized bed has been developed for the rapid recovery of malate dehydrogenase (MDH) from highly turbid baker's yeast cell homogenate in a single step. The most suitable dye, namely Reactive Orange 4, in its optimal immobilized concentration of 8.78 mg/mL was immobilized onto high-density STREAMLINE matrix. To further examine optimal adsorption and elution conditions, the enzyme recovery operation was carried out using unclarified cell homogenates in stirred fluidized bed system. Aiming to develop a non-specific eluent, namely NaCl, to effectively elute the MDH adsorbed, direct recovery of MDH from highly turbid cell homogenate (50% w/v) in a stirred fluidized bed adsorption system was performed. The proposed system successfully achieved a recovery yield of 73.6% and a purification factor of 73.5 in a single step by using 0.6 M NaCl as an eluent at a high liquid velocity of 200 cm/h.
    Matched MeSH terms: Saccharomyces cerevisiae/enzymology*
  6. Murugesu S, Ibrahim Z, Ahmed QU, Nik Yusoff NI, Uzir BF, Perumal V, et al.
    Molecules, 2018 Sep 19;23(9).
    PMID: 30235889 DOI: 10.3390/molecules23092402
    BACKGROUND: Clinacanthus nutans (C. nutans) is an Acanthaceae herbal shrub traditionally consumed to treat various diseases including diabetes in Malaysia. This study was designed to evaluate the α-glucosidase inhibitory activity of C. nutans leaves extracts, and to identify the metabolites responsible for the bioactivity.

    METHODS: Crude extract obtained from the dried leaves using 80% methanolic solution was further partitioned using different polarity solvents. The resultant extracts were investigated for their α-glucosidase inhibitory potential followed by metabolites profiling using the gas chromatography tandem with mass spectrometry (GC-MS).

    RESULTS: Multivariate data analysis was developed by correlating the bioactivity, and GC-MS data generated a suitable partial least square (PLS) model resulting in 11 bioactive compounds, namely, palmitic acid, phytol, hexadecanoic acid (methyl ester), 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol, glycerol monostearate, alpha-tocospiro B, and stigmasterol. In-silico study via molecular docking was carried out using the crystal structure Saccharomyces cerevisiae isomaltase (PDB code: 3A4A). Interactions between the inhibitors and the protein were predicted involving residues, namely LYS156, THR310, PRO312, LEU313, GLU411, and ASN415 with hydrogen bond, while PHE314 and ARG315 with hydrophobic bonding.

    CONCLUSION: The study provides informative data on the potential α-glucosidase inhibitors identified in C. nutans leaves, indicating the plant's therapeutic effect to manage hyperglycemia.

    Matched MeSH terms: Saccharomyces cerevisiae/enzymology
  7. Taha M, Shah SAA, Afifi M, Imran S, Sultan S, Rahim F, et al.
    Bioorg Chem, 2018 04;77:586-592.
    PMID: 29477126 DOI: 10.1016/j.bioorg.2018.01.033
    We have synthesized seventeen Coumarin based derivatives (1-17), characterized by 1HNMR, 13CNMR and EI-MS and evaluated for α-glucosidase inhibitory potential. Among the series, all derivatives exhibited outstanding α-glucosidase inhibition with IC50 values ranging between 1.10 ± 0.01 and 36.46 ± 0.70 μM when compared with the standard inhibitor acarbose having IC50 value 39.45 ± 0.10 μM. The most potent derivative among the series is derivative 3 having IC50 value 1.10 ± 0.01 μM, which are many folds better than the standard acarbose. The structure activity relationship (SAR) was mainly based upon by bring about difference of substituent's on phenyl part. Molecular docking studies were carried out to understand the binding interaction of the most active compounds.
    Matched MeSH terms: Saccharomyces cerevisiae/enzymology
  8. Ali F, Khan KM, Salar U, Taha M, Ismail NH, Wadood A, et al.
    Eur J Med Chem, 2017 Sep 29;138:255-272.
    PMID: 28672278 DOI: 10.1016/j.ejmech.2017.06.041
    Acarbose, miglitol, and voglibose are the inhibitors of α-glucosidase enzyme and being clinically used for the management of type-II diabetes mellitus. However, many adverse effects are also associated with them. So, the development of new therapeutic agents is an utmost interest in medicinal chemistry research. Current study is based on the identification of new α-glucosidase inhibitors. For that purpose, hydrazinyl arylthiazole based pyridine derivatives 1-39 were synthesized via two step reaction and fully characterized by spectroscopic techniques EI-MS, HREI-MS, (1)H-, and (13)C NMR. However, stereochemistry of the iminic bond was confirmed by NOESY. All compounds were subjected to in vitro α-glucosidase inhibitory activity and found many folds active (IC50 = 1.40 ± 0.01-236.10 ± 2.20 μM) as compared to the standard acarbose having IC50 value of 856.45 ± 5.60 μM. A limited structure-activity relationship was carried out in order to make a presumption about the substituent's effect on inhibitory activity which predicted that substituents of more negative inductive effect played important role in the activity as compared to the substituents of less negative inductive effect. However, in order to have a good understanding of ligand enzyme interactions, molecular docking study was also conducted. In silico study was confirmed that substituents like halogens (Cl) and nitro (NO2) which have negative inductive effect were found to make important interactions with active site residues.
    Matched MeSH terms: Saccharomyces cerevisiae/enzymology*
  9. Iftikhar M, Shahnawaz, Saleem M, Riaz N, Aziz-Ur-Rehman, Ahmed I, et al.
    Arch Pharm (Weinheim), 2019 Dec;352(12):e1900095.
    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: Saccharomyces cerevisiae/enzymology
  10. Ong SM, Voo LY, Lai NS, Stark MJ, Ho CC
    J Appl Microbiol, 2007 Mar;102(3):680-92.
    PMID: 17309617
    To identify novel microbial inhibitors of protein phosphatase 1 (PP1).
    Matched MeSH terms: Saccharomyces cerevisiae/enzymology
  11. Tariq QU, Malik S, Khan A, Naseer MM, Khan SU, Ashraf A, et al.
    Bioorg Chem, 2019 03;84:372-383.
    PMID: 30530108 DOI: 10.1016/j.bioorg.2018.11.053
    Xanthenone based hydrazone derivatives (5a-n) have been synthesized as potential α-glucosidase inhibitors. All synthesized compounds (5a-n) are characterized by their FTIR, 1H NMR, 13C NMR and HRMS, and in case of 5g also by X-ray crystallographic technique. The compounds unveiled a varying degree of α-glucosidase inhibitory activity when compared with standard acarbose (IC50 = 375.38 ± 0.12 µM). Amongst the series, compound 5l (IC50 = 62.25 ± 0.11 µM) bearing a trifluoromethyl phenyl group is found to be the most active compound. Molecular modelling is performed to establish the binding pattern of the more active compound 5l, which revealed the significance of substitution pattern. The pharmacological properties of molecules are also calculated by MedChem Designer which determines the ADME (absorption, distribution, metabolism, excretion) properties of molecules. The solid state self-assembly of compound 5g is discussed to show the conformation and role of iminoamide moiety in the molecular packing.
    Matched MeSH terms: Saccharomyces cerevisiae/enzymology
  12. Ruzlan N, Low YSJ, Win W, Azizah Musa N, Ong AL, Chew FT, et al.
    Sci Rep, 2017 08 29;7(1):9626.
    PMID: 28852058 DOI: 10.1038/s41598-017-10195-3
    The fructose-1,6-bisphosphate aldolase catalyzed glycolysis branch that forms dihydroxyacetone phosphate and glyceraldehyde-3-phosphate was identified as a key driver of increased oil synthesis in oil palm and was validated in Saccharomyces cerevisiae. Reduction in triose phosphate isomerase (TPI) activity in a yeast knockdown mutant resulted in 19% increase in lipid content, while yeast strains overexpressing oil palm fructose-1,6-bisphosphate aldolase (EgFBA) and glycerol-3-phosphate dehydrogenase (EgG3PDH) showed increased lipid content by 16% and 21%, respectively. Genetic association analysis on oil palm SNPs of EgTPI SD_SNP_000035801 and EgGAPDH SD_SNP_000041011 showed that palms harboring homozygous GG in EgTPI and heterozygous AG in EgGAPDH exhibited higher mesocarp oil content based on dry weight. In addition, AG genotype of the SNP of EgG3PDH SD_SNP_000008411 was associated with higher mean mesocarp oil content, whereas GG genotype of the EgFBA SNP SD_SNP_000007765 was favourable. Additive effects were observed with a combination of favourable alleles in TPI and FBA in Nigerian x AVROS population (family F7) with highest allele frequency GG.GG being associated with a mean increase of 3.77% (p value = 2.3E-16) oil content over the Family 1. An analogous effect was observed in yeast, where overexpressed EgFBA in TPI - resulted in a 30% oil increment. These results provide insights into flux balances in glycolysis leading to higher yield in mesocarp oil-producing fruit.
    Matched MeSH terms: Saccharomyces cerevisiae/enzymology
Filters
Contact Us

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

External Links