Social and Behavioral Sciences Commons^™

Synthesis Of 3-Halo-2,5-Disubstituted Furans Via Cux Mediated Cyclization-Halogenation Reactions, Arife Yazici, Stephen G. Pyne

Faculty of Science - Papers (Archive)

The Cu(I) halide (X = I, Br, Cl) mediated reactions of Cbz-protected cis-2-phenylethenyl-3-hydroxypyrrolidine gave novel 3-halo-2,5-trisubstituted furans in good yields, via a cyclization-halogenation, ring-opening reaction sequence. In contrast, the reactions with CuCN gave mainly the corresponding 3-cyanofuro[3,2-b]pyrrole formed from a cyclization-cyanation reaction.

An Unusually Flexible Expanded Hexaamine Cage And Its Cuii Complexes: Variable Coordination Modes And Incomplete Encapsulation, C-J Qin, Lloyd James, Jy D. Chartres, Leighton J. Alcock, Kimberley J. Davis, Anthony C. Willis, Alan M. Sargeson, Paul V. Bernhardt, Stephen F. Ralph

Faculty of Science - Papers (Archive)

The bicyclic hexaamine "cage" ligand Me 8tricosaneN 6 (1,5,5,9,13,13,20,20-octamethyl-3,7,11,15,18, 22-hexaazabicyclo[7.7.7]tricosane) is capable of encapsulating octahedral metal ions, yet its expanded cavity allows the complexed metal to adopt a variety of geometries comprising either hexadentate or pentadentate coordination of the ligand. When complexed to Cu II the lability of the metal results in a dynamic equilibrium in solution between hexadentate- and pentadentate- coordinated complexes of Me 8tricosaneN 6. Both [Cu(Me 8tricosaneN 6)](ClO 4) 2 (6-coordinate) and [Cu(Me 8tricosaneN 6)](S 2O 6) (5-coordinate) have been characterized structurally. In weak acid (pH 1) a singly protonated complex [Cu(HMe 8tricosaneN 6)] 3+ has been …

Synthesis And Structural Characterization Of 1-[2-(5-Nitro-1h-Indol-2-Yl)Phenyl]Methylpyridinium Chloride, John B. Bremner, Siritron Samosorn, Brian W. Skelton, Allan White

Faculty of Science - Papers (Archive)

In the course of studies on hybrid antibacterials incorporating 2-aryl-5-nitro-1Hindolemoieties as potential bacterial NorA efflux pump inhibitors, the compound 1-[2-(5-nitro-1H-indol-2-yl)phenyl]methylpyridinium chloride (2) was synthesized and structurallycharacterized. This pyridinium chloride salt crystallized in the monoclinic space groupP21/c with the following unit cell dimensions: a 10.274(3) A, b 13.101(4) A, c 13.439(4)A, B 107.702(7)deg, V 1723.2(9) A3, Z (f.u.) = 4; R1 = 0.048, and wR2 = 0.13. Of interest inthe single crystal X-ray structure is the (intramolecular) disposition of the pyridinium planeover the indole heterocyclic residue [interplanar dihedral angle 17.91(4)deg].

Nanoesi Mass Spectrometry Of Rubisco And Rubisco Activase Structures And Their Interactions With Nucleotides And Sugar Phosphates, Michelle Blayney, Spencer M. Whitney, Jennifer L. Beck

Faculty of Science - Papers (Archive)

Ribulose bisphosphate carboxylase/oxygenase (Rubisco) is the protein that is responsible for the fixation of carbon dioxide in photosynthesis. Inhibitory sugar phosphate molecules, which can include its substrate ribulose-1,5- bisphosphate (RuBP), can bind to Rubisco catalytic sites and inhibit catalysis. These are removed by interaction with Rubisco activase (RA) via an ATP hydrolytic reaction. Here we show the first nanoESI mass spectra of the hexadecameric Rubisco and of RA from a higher plant (tobacco). The spectra of recombinant, purified RA revealed polydispersity in its oligomeric forms (up to hexamer) and that ADP was bound. ADP was removed by dialysis against a …

Clusterin Facilitates In Vivo Clearance Of Extracellular Misfolded Proteins, Amy R. Wyatt, Justin J. Yerbury, Paula Berghofer, I Greguric, Andrew Katsifis, Christopher Dobson, Mark R. Wilson

Faculty of Science - Papers (Archive)

The extracellular deposition of misfolded proteins is a characteristic of many debilitating age-related disorders. However, little is known about the specific mechanisms that act to suppress this process in vivo. Clusterin (CLU) is an extracellular chaperone that forms stable and soluble complexes with misfolded client proteins. Here we explore the fate of complexes formed between CLU and misfolded proteins both in vitro and in a living organism. We show that proteins injected into rats are cleared more rapidly from circulation when complexed with CLU as a result of their more efficient localisation to the liver and that this clearance …

Antimalarial, Anticancer, Antimicrobial Activities And Chemical Constituents Of Essential Oil From The Aerial Parts Of Cyperus Kyllingia Endl, Stephen G. Pyne, Boonsom Liawruangrath, Saisunee Liawruangrath, M Garson, S Khamsan, A Teerawutkulrag

Faculty of Science - Papers (Archive)

The chemical constituents of the essential oil from Cyperus kyllingia Endl. were analyzed by a GC, GC-MS. Twenty-three compounds were identified, accounting for 93.75% of the total oil that consisted mainly of oxygenated sesquiterpenes (53.52%), particularly sesquiterpene hydrocarbons (38.97%), and carboxylic acid (1.26%). The most representative compounds were -cadinol (19.32%), caryophyllene oxide (12.17%), -muurolol (11.58%), -humulene (9.85%), and -atlantone (6.07%). The oil showed significant activities against Plasmodium falcipalum (K1, multi drug resistant strain) and NCI-H187 (Small Cell Lung Cancer) with the IC50 values of 7.52 and 7.72 g/mL, respectively. The oil exhibited highly active against Staphylococcus aureus ATCC25923 and moderately …

Synthesis And Preliminary Evaluation Of Amiloride Analogs As Inhibitors Of The Urokinase-Type Plasminogen Activator (Upa), Hayden Matthews, Marie Ranson, Joel Tyndall, Michael J. Kelso

Faculty of Science - Papers (Archive)

A known side-activity of the oral potassium-sparing diuretic drug amiloride is inhibition of the enzyme urokinase-type plasminogen activator (uPA, K_i = 7 mu M), a promising anticancer target. Several studies have demonstrated significant antitumor/metastasis properties for amiloride in animal cancer models and it would appear that these arise, at least in part, through inhibition of uPA. Selective optimization of amiloride’s structure for more potent inhibition of uPA and loss of diuretic effects would thus appear as an attractive strategy towards novel anticancer agents. The following report is a preliminary structure-activity exploration of amiloride analogs as inhibitors of uPA. A …

Poly(T) Variation In Heteroderid Nematode Mitochondrial Genomes Is Predominantly An Artefact Of Amplification, Angelique H. Riepsamen, Tracey A. Gibson, Janet Rowe, David J. Chitwood, Sergei Subbotin, Mark P. Dowton

Faculty of Science - Papers (Archive)

We assessed the rate of in vitro polymerase errors at polythymidine [poly(T)] tracts in the mitochondrial DNA (mtDNA) of a heteroderid nematode (Heterodera cajani). The mtDNA of these nematodes contain unusually high numbers of poly(T) tracts, and have previously been suggested to contain biological poly(T) length variation. However, using a cloned molecule, we observed that poly(T) variation was generated in vitro at regions containing more than six consecutive Ts. This artefactual error rate was estimated at 7.3 × 10−5 indels/poly(T) tract >6 Ts/cycle. This rate was then compared to the rate of poly(T) variation detected after the amplification of a …

Stereoselective Synthesis Of Two New Trihydroxylated Pyrrolidines Using A Meyer-Schuster Rearrangement, Nalivela K. Swamy, Stephen G. Pyne

Faculty of Science - Papers (Archive)

The synthesis of two new trihydroxylated pyrrolidines, in a highly diastereoselective manner, has been developed using the Meyer-Schuster rearrangement as a key step. C 2011 Taylor & Francis Group, LLC.

Wild Type And Tangier Disease Abca1 Mutants Modulate Cellular Amyloid-Beta Production Independent Of Cholesterol Efflux Activity, Kim S. Woojin, Andrew F. Hill, Michael L. Fitzgerald, Mason W. Freeman, Genevieve Evin, Brett Garner

Faculty of Science - Papers (Archive)

Cerebral amyloid-β (Aβ) deposition is a critical feature of Alzheimer’s disease. Aβ is derived from the amyloid-β protein precursor (AβPP) via two sequential cleavages that are mediated by β-secretase and the γ-secretase complex. Such amyloidogenic AβPP processing occurs in lipid raft microdomains of cell membranes and it is thought that modulating the distribution of lipids in rafts may regulate AβPP processing and Aβ production. Certain ATP-binding cassette (ABC) transporters regulate lipid transport across cell membranes and, as recent studies reveal, within membrane microdomains. ABCA1 also regulates Aβ metabolism in the brain although its direct impact on AβPP remains an open …

Corrigendum To ‘‘The Chaperone Action Of Bovine Milk As1- And As2-Caseins And Their Associated Form As-Casein’’ [Arch. Biochem. Biophys. 510 (2011) 42–52], Teresa M. Treweek, David C. Thorn, William E. Price, John A. Carver

Faculty of Science - Papers (Archive)

No abstract provided.

Incorporation Of Chlorinated Analogues Of Aliphatic Amino Acids During Cell-Free Protein Synthesis, Dannon J. Stigers, Zachary I. Watts, James E. Hennessy, Hye-Kyung Kim, Romeo Martini, Matthew C. Taylor, Kiyoshi Ozawa, Jeffrey W. Keillor, Nicholas E. Dixon, Christopher J. Easton

Faculty of Science - Papers (Archive)

3-Chloro-Abu and 4-chloro-Nva are biosynthetically incorporated into E. coli peptidyl-Pro cis-trans isomerase B, as substitutes for Val and Leu, respectively. The extent of incorporation is up to 90%, and substituted protein is catalytically active. By contrast, 4-chloro-Val is not an effective replacement for Ile.

Kinase Inhibitors From Marine Sponges, Danielle Skropeta, Natalie Pastro, Ana Zivanovic

Faculty of Science - Papers (Archive)

Protein kinases play a critical role in cell regulation and their deregulation is a contributing factor in an increasing list of diseases including cancer. Marine sponges have yielded over 70 novel compounds to date that exhibit significant inhibitory activity towards a range of protein kinases. These compounds, which belong to diverse structural classes, are reviewed herein, and ordered based upon the kinase that they inhibit. Relevant synthetic studies on the marine natural product kinase inhibitors have also been included.

Glutathione Transferases: A Structural Perspective, Aaron J. Oakley

Faculty of Science - Papers (Archive)

The glutathione transferases (GSTs) are one of the most important families of detoxifying enzymes in nature. The classic activity of the GSTs is conjugation of compounds with electrophilic centers to the tripeptide glutathione (GSH), but many other activities are now associated with GSTs, including steroid and leukotriene biosynthesis, peroxide degradation, double-bond cis-trans isomerization, dehydroascorbate reduction, Michael addition, and noncatalytic “ligandin” activity (ligand binding and transport). Since the first GST structure was determined in 1991, there has been an explosion in structural data across GSTs of all three families: the cytosolic GSTs, the mitochondrial GSTs, and the membrane-associated proteins in eicosanoid …

Kinase Inhibitory, Haemolytic And Cytotoxic Activity Of Three Deep-Water Sponges From North Western Australia And Their Fatty Acid Composition, Ana Zivanovic, Natalie J. Pastro, Jane Fromont, Murray Thomson, Danielle Skropeta

Faculty of Science - Papers (Archive)

The c-AMP dependent protein kinase (PKA) inhibition, haemolytic activity, and cytoxicity of 21 extracts obtained from North Western Australian sponges collected from depths of 84-135 m were investigated. Hexane extracts from Ircinia/Sarcotragus sp. and Geodia sp. displayed PKA inhibitory activities of 100 and 97% respectively (at 100 μg/mL), while aq. methanol extracts from Haliclona sp. exhibited potent haemolytic activity (75%) and hexane extracts from Geodia sp. were highly toxic (88%) to the brine shrimp Artemia franciscana. As the non-polar extracts gave the greatest PKA inhibition, these were further analysed by GC-MS and 29 fatty acids were identified in the highest …

Lipid Pathway Alterations In Parkinson's Disease Primary Visual Cortex, Danni Cheng, Andrew M. Jenner, Guanghou Shui, Wei Fun Cheong, Todd W. Mitchell, Jessica Nealon, Woojin Scott Kim, H Mccann, Markus R. Wenk, Glenda Halliday, Brett Garner

Faculty of Science - Papers (Archive)

Background: We present a lipidomics analysis of human Parkinson’s disease tissues. We have focused on the primary visual cortex, a region that is devoid of pathological changes and Lewy bodies; and two additional regions, the amygdala and anterior cingulate cortex which contain Lewy bodies at different disease stages but do not have as severe degeneration as the substantia nigra. Methodology/Principal Findings: Using liquid chromatography mass spectrometry lipidomics techniques for an initial screen of 200 lipid species, significant changes in 79 sphingolipid, glycerophospholipid and cholesterol species were detected in the visual cortex of Parkinson’s disease patients (n = 10) compared to …

Ion Selectivity In Channels And Transporters, Benoit Roux, Simon Berneche, Berhard Egwolf, Bogdan Lev, Sergei Y. Noskov, Christopher N. Rowley, Haibo Yu

Faculty of Science - Papers (Archive)

No abstract provided.

Significance Of P2x7 Receptor Variants To Human Health And Disease, Ronald Sluyter, Leanne Stokes

Faculty of Science - Papers (Archive)

The human P2X7 receptor is a trimeric ligand-gated cation channel coded by the P2RX7 gene located at chromosome position 12q24. P2X7 is expressed in a wide variety of normal and disease-associated cell types. Activation of this receptor by extracellular adenosine 5’-triphosphate results in numerous downstream events including the release of pro-inflammatory mediators, cell proliferation or death, and killing of intracellular pathogens. As a result, P2X7 plays important roles in inflammation, immunity, bone homeostasis, neurological function and neoplasia. The P2RX7 gene encodes a P2X7 subunit 595 amino acids in length, however splice isoforms that can alter receptor expression and function, and …

Influence Of Salicylic Acid On Alkaloid Production By Root Cultures Of Stemona Curtisii Hook. F., K. Chotikadachanarong, S. Dheeranupattana, Chaiwat Jatisatienr, S. Wangkarn, Pitchaya Mungkornasawakul, Stephen G. Pyne, Alison T. Ung, Thanapat Sastraruji

Faculty of Science - Papers (Archive)

To enhance the production of oxyprotostemonine, stemocurtisine and stemocurtisinol (the important insecticidal alkaloids) by root cultures of Stemona curtisii Hook. F. (Thai vernacular, Non Tai Yak, Family Stemonaceae). The roots were cultured on semi-solid MS medium containing 1 mg/L NAA with different concentrations of salicylic acid for 16 weeks. The quantity of the individual alkaloids was determined by HPLC. The highest production of oxyprotostemonine (7.192 mg/g dw), stemocurtisine (0.039 mg/g dw) and stemocurtisinol (0.197 mg/g dw) occurred when the roots were stimulated by 500 mg/L salicylic acid.

Phytochemical Studies On Stemona Aphylla: Isolation Of A New Stemofoline Alkaloid And Six New Stemofurans, Thanapat Sastraruji, Sukanda Chaiyong, Araya Jatisatienr, Stephen G. Pyne, Alison T. Ung, Wilford Lie

Faculty of Science - Papers (Archive)

A new stemofoline alkaloid, (2′S)-hydroxy-(11S,12R)-dihydrostemofoline (3), new stemofurans M-R (8-13), and known compounds stemofoline (1), (2′S)-hydroxystemofoline (2), stemofuran E (4), stemofuran F (5), stemofuran J (6), and stilbostemin F (7) have been isolated from the root extracts of Stemona aphylla. The structures and relative configurations of these new compounds have been determined by spectroscopic data interpretation and from semisynthetic studies. These natural and semisynthetic alkaloids were tested for acetylcholinesterase inhibitory activities and were found to be 10-20 times less active than 1′,2′-didehydrostemofoline itself. Stemofurans 4, 6, 8, 11, and 13 were tested for their antibacterial and antifungal activities. Three of …

Understanding The Α-Crystallin Cell Membrane Conjunction, Shih-Ping Su, Jason D. Mcarthur, Michael G. Friedrich, Roger J. W Truscott, J. A. Aquilina

Faculty of Science - Papers (Archive)

PURPOSE. It is well established that levels of soluble α-crystallin in the lens cytoplasm fall steadily with age, accompanied by a corresponding increase in the amount of membrane-bound α-crystallin. Less well understood, is the mechanism driving this age-dependent membrane association. The aim of this study was to investigate the role of the membrane and its associated proteins and peptides in the binding of α-crystallin.

METHODS. Fibre cell membranes from human and bovine lenses were separated from soluble proteins by centrifugation. Membranes were stripped of associated proteins with successive aqueous, urea and alkaline solutions. Protein constituents of the respective membrane isolates …

Revealing Indigenous Indonesian Traditional Medicine: Anti-Infective Agents, Paul A. Keller, Ari Satia Nugraha

Faculty of Science - Papers (Archive)

Indonesia is rich in medicinal plants which the population has used traditionally from generation to generation for curing diseases. Our interest in the treatment of infectious diseases has lead to the investigation of traditional Indonesian treatments. In this review, we present a comprehensive review of ethnopharmacologically directed screening in Indonesian medicinal plants to search for new anti-viral, antimalarial, anti-bacterial and anti-fungal agents. Some potent drug leads have been isolated from Indonesian medicinal plants. Further research is still required for the lead development as well as the search for new bioactive compounds from the enormous medicinal plant resources.

Isolation Of Linobiflavonoid, A Novel Biflavonoid From Linostoma Pauciflorum Griff, Tawesin Navarat, Stephen G. Pyne, Uma Prawat, Pittaya Tuntiwachwuttikul

Faculty of Science - Papers (Archive)

A novel biflavonoid, that we have named linobiflavonoid, and the known biscoumarin ether, daphnoretin, were isolated from the root extracts of Linostoma pauciflorum Griff. The structure of linobiflavonoid was determined from interpretation of its NMR spectroscopic data and from a comparison of this data with those of known biflavonoids and biflavones. The known flavones, 5,4'-dihydroxy- 7,3',5'-trimethoxyflavone and 5,4'-dihydroxy-7-methoxyflavone along with stigmasterol were isolated from the vines of the same plant. 4'-Dihydroxy-7,3'-5'-trimethoxyflavone was active against Mycobacterium tuberculosis (MIC 3.13 mu M) and KB-oral cavity cancer (IC₅₀ 17.41 mu M). (C) 2011 Phytochemical Society of Europe. Published by Elsevier B.V. All …

Binding Of The Molecular Chaperone Alphab-Crystallin To Abeta Amyloid Fibrils Inhibits Fibril Elongation, Sarah L. Shammas, Christopher A. Waudby, Shuyu Wang, Alexander K. Buell, Tuomas P. Knowles, Heath W. Ecroyd, Mark E. Welland, John A. Carver, Christopher M. Dobson, Sarah Meehan

Faculty of Science - Papers (Archive)

The molecular chaperone αB-crystallin is a small heat-shock protein that is upregulated in response to a multitude of stress stimuli, and is found colocalized with Aβ amyloid fibrils in the extracellular plaques that are characteristic of Alzheimer's disease. We investigated whether this archetypical small heat-shock protein has the ability to interact with Aβ fibrils in vitro. We find that αB-crystallin binds to wild-type Aβ₄₂ fibrils with micromolar affinity, and also binds to fibrils formed from the E22G Arctic mutation of Aβ₄₂. Immunoelectron microscopy confirms that binding occurs along the entire length …

Identification Of Phospholipids In Human Meibum By Nano-Electrospray Ionisation Tandem Mass Spectrometry, Jennifer T. Saville, Zhenjun Zhao, Mark Dp Willcox, Manjula A. Ariyavidana, Stephen J. Blanksby, Todd W. Mitchell

Faculty of Science - Papers (Archive)

Meibum is believed to be the major source of tear !lm lipids, which are vital in the prevention of excessevaporation of the aqueous phase. The complete lipid composition of meibum has yet to be established.While earlier studies reported the presence of phospholipids in human meibum, recent mass spectrometricstudies have not detected them. In this study we use electrospray ionisation tandem massspectrometry to investigate the presence of phospholipids in meibum and provide comparison to thephospholipid pro!le of tears.Lipids were extracted from human meibum and tear samples using standard biphasic methods andanalysed by nano-electrospray ionisation tandem mass spectrometry using targeted ion scans. …

Speciation Of Dissolved Inorganic Arsenic By Diffusive Gradients In Thin Films: Selective Binding Of Asiii By 3-Mercaptopropyl-Functionalized Silica Gel, William W. Bennett, Peter R. Teasdale, Jarad G. Panther, David T. Welsh, Dianne F. Jolley

Faculty of Science - Papers (Archive)

A diffusive gradients in thin films (DGT) technique for selectively measuring AsIII utilizes commercially available 3-mercaptopropyl- functionalized silica gel. Deployment of the new technique alongside the Metsorb-DGT for total inorganic arsenic allows the calculation of As III directly and AsV by difference. Uptake of As III by mercapto-silica was quantitative and elution with a mixture of 1 mol L-1 HNO3 and 0.01 mol L-1 KIO 3 gave a recovery of 85.6 + 1.7%. DGT validation experiments showed linear accumulation of AsIII over time (R2 > 0.998). Accumulation was unaffected by varying ionic strength (0.0001-0.75 mol L-1 NaNO3) and pH (3.5-8.5). Deployment …

An Assessment Of Three Harpacticoid Copepod Species For Use In Ecotoxicological Testing, Daniel J. Ward, Victor Perez-Landa, David A. Spadaro, Stuart L. Simpson, Dianne F. Jolley

Faculty of Science - Papers (Archive)

The relatively short life cycles of harpacticoid copepods makes them appropriate animals for use in tests that rapidly assess the #180, sublethal, or chronic effects of sediment contaminants. In this study, four harpacticoid copepod species (Nitocra spinipes, Tisbe tenuimana, Robertgurneya hopkinsi, and Halectinosoma sp.) were isolated from clean marine sediments, and procedures for laboratory culturing were developed. Halectinosoma sp. was abandoned due to handling difficulties. For the remaining species, the influence of food type and quantity on life-cycle progression was assessed. A mixed diet, comprising two species of algae (Tetraselmis sp. and Isochrysis sp.) and fish food (Sera …