Social and Behavioral Sciences Commons^™

Structural And Thermodynamic Dissection Of Linear Motif Recognition By The E. Coli Sliding Clamp, Zhou Yin, Michael J. Kelso, Jennifer L. Beck, Aaron J. Oakley

Faculty of Science, Medicine and Health - Papers: part A

Protein-protein interactions based on linear motif (LM) recognition play roles in many cell regulatory processes. The E. coli sliding clamp is a protein mediator of replisome formation, which uses a common surface pocket composed of two subsites (I and II) to interact with LMs in multiple binding partners. A structural and thermodynamic dissection of sliding clamp-LM recognition has been performed, providing support for a sequential binding model. According to the model, a hydrophobic C-terminal LM dipeptide submotif acts as an anchor to establish initial contacts within subsite I, and this is followed by formation of a stabilizing hydrogen-bonding network between …

Theoretical Study On The Ring-Opening Reactions Of Cyclopropenes Mediated By A Aui Complex, Nasir Ahmad Rajabi, Mona Jalali Atashgah, Rasool Babaahmadi, Christopher Hyland, Alireza Ariafard

Faculty of Science, Medicine and Health - Papers: part A

DFT calculations have been carried out in order to rationalize and predict the ring-opening regioselectivity of substituted cyclopropenes in the presence of gold(I) catalysts. It has been shown that the regioselectivity of these ring-opening processes is driven by the relative π-donor ability of the substituents on the cyclopropene double bond (C1 and C2). A stronger π-donor substituent at C2 favors Au(I)-induced polarization of the double bond toward C1, resulting in preferential breaking of the C1–C3 bond. An excellent correlation between ΔE and the difference in the C1–C2 p(π) orbital population was observed for a broad range of substituents, providing a …

The Role Of Ghrelin Signalling In Second-Generation Antipsychotic-Induced Weight Gain, Qingsheng Zhang, Chao Deng, Xu-Feng Huang

Faculty of Science, Medicine and Health - Papers: part A

Based on clinical and animal studies, this review suggests a tri-phasic effect of second-generation antipsychotics (SGAs) on circulating ghrelin levels: an initial increase exerted by the acute effect of SGAs; followed by a secondary decrease possibly due to the negative feedback from the SGA-induced body weight gain or hyperphagia; and a final re-increase to reach the new equilibrium. Moreover, the results can also vary depending on individual SGAs, other hormonal states, dietary choices, and other confounding factors including medical history, co-treatments, age, gender, and ghrelin measurement techniques. Interestingly, rats treated with olanzapine, an SGA with high weight gain liabilities, are …

6-Hydroxy-5,6-Seco-Stemocurtisine: A Novel Seco-Stemocurtisine-Type Alkaloid, Pitchaya Mungkornasawakul, Stephen G. Pyne, Anthony C. Willis, Araya Jatisatienr, Duang Phuthsuk, Wilford Lie

Faculty of Science, Medicine and Health - Papers: part A

A novel seco-stemocurtisine-type alkaloid, 6-hydroxy-5,6-seco-stemocurtisine was isolated from the aerial parts of Stemona curtisii (Stemonaceae) collected from Trang Province in Thailand. The unprecedented 5,6-seco-pyrido[1,2-a] azepine structure was elucidated by 2D NMR analysis and a single crystal X-ray crystallographic analysis. (C) 2013 Phytochemical Society of Europe.

The Small Heat Shock Proteins Αb-Crystallin And Hsp27 Suppress Sod1 Aggregation In Vitro, Justin J. Yerbury, Dane Gower, Laura Vanags, Kate Roberts, Jodi A. Lee, Heath Ecroyd

Faculty of Science, Medicine and Health - Papers: part A

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease. The mechanism that underlies amyotrophic lateral sclerosis (ALS) pathology remains unclear, but protein inclusions are associated with all forms of the disease. Apart from pathogenic proteins, such as TDP-43 and SOD1, other proteins are associated with ALS inclusions including small heat shock proteins. However, whether small heat shock proteins have a direct effect on SOD1 aggregation remains unknown. In this study, we have examined the ability of small heat shock proteins αB-crystallin and Hsp27 to inhibit the aggregation of SOD1 in vitro. We show that these chaperone proteins suppress the increase in …

Extracellular Chaperones, Rebecca A. Dabbs, Amy R. Wyatt, Justin J. Yerbury, Heath Ecroyd, Mark R. Wilson

Faculty of Science, Medicine and Health - Papers: part A

The maintenance of the levels and correct folding state of proteins (proteostasis) is a fundamental prerequisite for life. Life has evolved complex mechanisms to maintain proteostasis and many of these that operate inside cells are now well understood. The same cannot yet be said of corresponding processes in extracellular fluids of the human body, where inappropriate protein aggregation is known to underpin many serious diseases such as Alzheimer's disease, type II diabetes and prion diseases. Recent research has uncovered a growing family of abundant extracellular chaperones in body fluids which appear to selectively bind to exposed regions of hydrophobicity on …

Deletion Of Abca7 Increases Cerebral Amyloid-Β Accumulation In The J20 Mouse Model Of Alzheimer's Disease, Woojin S. Kim, Hongyun Li, Kalani Ruberu, Sharon Chan, David A. Elliott, Jac Kee Low, David Cheng, Tim Karl, Brett Garner

Faculty of Science, Medicine and Health - Papers: part A

ATP-binding cassette transporter A7 (ABCA7) is expressed in the brain and has been detected in macrophages, microglia, and neurons. ABCA7 promotes efflux of lipids from cells to apolipoproteins and can also regulate phagocytosis and modulate processing of amyloid precursor protein (APP) to generate the Alzheimer's disease (AD) amyloid-β (Aβ) peptide. Genome-wide association studies have indicated that ABCA7 single nucleotide polymorphisms confer increased risk for late-onset AD; however, the role that ABCA7 plays in the brain in the AD context is unknown. In the present study, we crossed ABCA7-deficient (A7-/-) mice with J20 amyloidogenic mice to address this issue. We show …

Structural Insights Into Omega-Class Glutathione Transferases: A Snapshot Of Enzyme Reduction And Identification Of A Non-Catalytic Ligandin Site, Joseph Brock, Philip G. Board, Aaron J. Oakley

Faculty of Science, Medicine and Health - Papers: part A

Glutathione transferases (GSTs) are dimeric enzymes containing one active-site per monomer. The omega-class GSTs (hGSTO1-1 and hGSTO2-2 in humans) are homodimeric and carry out a range of reactions including the glutathione-dependant reduction of a range of compounds and the reduction of S-(phenacyl)glutathiones to acetophenones. Both types of reaction result in the formation of a mixed-disulfide of the enzyme with glutathione through the catalytic cysteine (C32). Recycling of the enzyme utilizes a second glutathione molecule and results in oxidized glutathione (GSSG) release. The crystal structure of an active-site mutant (C32A) of the hGSTO1-1 isozyme in complex with GSSG provides a snapshot …

Inhibition Of P-Glycoprotein Mediated Multidrug Resistance By Stemofoline Derivatives, Sonthaya Umsumarng, Komsak Pintha, Pornsiri Pitchakarn, Kwankamol Sastraruji, Thanapat Sastraruji, Alison T. Ung, Araya Jatisatienr, Stephen G. Pyne, Pornngarm Limtrakul

Faculty of Science, Medicine and Health - Papers: part A

Resistance to chemotherapy in cancer patients has been correlated to the overexpression of the ATP-binding cassette (ABC) drug transporters including P-glycoprotein (P-gp) that actively efflux chemotherapeutic drugs from cancer cells. We examined the mutidrug resistance reversing property of stemofoline derivatives in drug-resistance human cervical carcinoma (KB-V1) and human leukemic (K562/Adr) cell lines that overexpress P-gp. Didehydrostemofoline and eleven of its derivatives were synthesized and the cytotoxicity and their effect on doxorubicin, vinblastine and paclitaxel sensitivity in drug resistant (KB-V1 and K562/Adr) and drug sensitive (KB-3-1 and K562) cell lines by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were determined. We found that …

Rapid Differentiation Of Isomeric Lipids By Photodissociation Mass Spectrometry Of Fatty Acid Derivatives, Huong T. Pham, Adam J. Trevitt, Todd W. Mitchell, Stephen J. Blanksby

Faculty of Science, Medicine and Health - Papers: part A

RATIONALE Both traditional electron ionization and electrospray ionization tandem mass spectrometry have demonstrated limitations in the unambiguous identification of fatty acids. In the former case, high electron energies lead to extensive dissociation of the radical cations from which little specific structural information can be obtained. In the latter, conventional collision-induced dissociation (CID) of even-electron ions provides little intra-chain fragmentation and thus few structural diagnostics. New approaches that harness the desirable features of both methods, namely radical-driven dissociation with discrete energy deposition, are thus required.

METHODS Herein we describe the derivatization of a structurally diverse suite of fatty acids as 4-iodobenzyl …

Cytoprotective Properties Of Traditional Chinese Medicinal Herbal Extracts In Hydrogen Peroxide Challenged Human U373 Astroglia Cells, Megan L. Steele, John Truong, Suresh Govindaraghavan, Lezanne Ooi, Nikolaus J. Sucher, Gerald Munch

Faculty of Science, Medicine and Health - Papers: part A

Age is the leading risk factor for many of the most prevalent and devastating diseases including neurodegenerative diseases. A number of herbal medicines have been used for centuries to ameliorate the deleterious effects of ageing-related diseases and increase longevity. Oxidative stress is believed to play a role in normal ageing as well as in neurodegenerative processes. Since many of the constituents of herbal extracts are known antioxidants, it is believed that restoring oxidative balance may be one of the underlying mechanisms by which medicinal herbs can protect against ageing and cognitive decline. Based on the premise that astrocytes are key …

Triple Cysteine Module Within M-Type K+ Channels Mediates Reciprocal Channel Modulation By Nitric Oxide And Reactive Oxygen Species, Lezanne Ooi, Sylvain Gigout, Louisa Pettinger, Nikita Gamper

Faculty of Science, Medicine and Health - Papers: part A

We have identified a new signaling role for nitric oxide (NO) in neurons from the trigeminal ganglia (TG). We show that in rat sensory neurons from the TG the NO donor, S-nitroso-N-acetyl-dl-penicillamine, inhibited M-current. This inhibitory effect was blocked by NO scavenging, while inhibition of NO synthases increased M-current, suggesting that tonic NO levels inhibit M-current in TG neurons. Moreover NO increased neuronal excitability and calcitonin gene-related peptide (CGRP) release and these effects could be prevented by perturbing M-channel function. First, NO-induced depolarization was prevented by pre-application of the M-channel blocker XE991 and second, NO-induced increase in CGRP release was …

The Association Of Antidepressant Medication And Body Weight Gain, Sara Ranjbar, Nagesh B. Pai, Chao Deng

Faculty of Science, Medicine and Health - Papers: part A

Objective: To review the literature and discover which antidepressants are responsible for weight gain and then to discuss the areas with lack of adequate knowledge.

Method: An electronic search was conducted through Medline, Pubmed, Cochrane library, and ScienceDirect. Forty nine empirical researches were identified and reviewed.

Results: Amitriptyline, clomipramine, and mirtazapine have been associated with more weight gain induction in clinical studies, but not in animal-based studies. All TCAs have been reported to cause weight gain except protriptyline. MAOIs have been associated with weight gain. In SSRI group, citalopram and ecitalopram induce weight, yet mixed results exist for paroxetine and …

Metabotropic Glutamate Receptor 5 Binding And Protein Expression In Schizophrenia And Following Antipsychotic Drug Treatment, Natalie Matosin, Elisabeth Frank, Chao Deng, Xu-Feng Huang, Kelly A. Newell

Faculty of Science, Medicine and Health - Papers: part A

Metabotropic glutamate receptor 5 (mGluR5) has been identified as a potential therapeutic target for schizophrenia, primarily due to its ability to indirectly modulate glutamatergic signalling through the NMDA receptor (NMDAR). Despite its potential, molecular studies characterising mGluR5 in schizophrenia are limited. We therefore aimed to determine if the mGluR5 binding site or protein levels were altered in schizophrenia or by current antipsychotics. Using in-situ radioligand binding and immunoblot, we measured [3H]MPEP binding to mGluR5 and mGluR5 protein density in the post-mortem dorsolateral prefrontal cortex (DLPFC; BA46) of 37 schizophrenia and 37 matched control subjects. Subsequently, we measured [3H]MPEP binding in …

Synthesis Of Cephalosporin-3′-Diazeniumdiolates: Biofilm Dispersing No-Donor Prodrugs Activated By Β-Lactamase, Nageshwar Rao Yepuri, Nicolas Barraud, Nasim Shah Mohammadi, Bharat G. Kardak, Staffan Kjelleberg, Scott A. Rice, Michael J. Kelso

Faculty of Science, Medicine and Health - Papers: part A

Use of biofilm dispersing NO-donor compounds in combination with antibiotics has emerged as a promising new strategy for treating drug-resistant bacterial biofilm infections. This paper details the synthesis and preliminary evaluation of six cephalosporin-3′-diazeniumdiolates as biofilm-targeted NO-donor prodrugs. Each of the compounds is shown to selectively release NO following reaction with the bacteria-specific enzyme β-lactamase and to trigger dispersion of Pseudomonas aeruginosa biofilms in vitro.

Synthesis And Inhibitory Activities At Mglurs Of 3-Alkylated And N-Alkylated Cyclopentyl-Glutamate Analogues, Alison T. Ung, Stephen G. Pyne, Francois Bischoff, Anne S. J Lesage, Brian W. Skelton, Allan H. White

Faculty of Science, Medicine and Health - Papers: part A

The conformationally restricted glutamate analogues, 3-alkyl-1-amino-2-cyclopentene-1,3-dicarboxylates and N-alkylated analogues have been prepared in a regioselective and diastereoselective manner. From the biological studies of the 3-alkylated analogues, compound 13b was found to be the most potent antagonist (IC50 7.7 μM) at mGluR2. Amongst the N-alkylated analogues, compound 20 was found to be a partial agonist (EC50 9.5 μM) and as well as an antagonist (IC50 47 μM) at mGluR2.

Removal Of Trace Organic Contaminants By Nitrifying Activated Sludge And Whole-Cell And Crude Enzyme Extract Of Trametes Versicolor, Shufan Yang, Faisal I. Hai, Long D. Nghiem, Felicity Roddick, William E. Price

Faculty of Science, Medicine and Health - Papers: part A

The resistance of certain anthropogenic trace organic contaminants (TrOCs) to conventional wastewater treatment and their potential adverse effects on human and ecological health raise significant concerns and have prompted research on their bioremediation by white-rot fungi. This study compared the removal efficiencies of four widespread TrOCs: carbamazepine (CBZ), sulfamethoxazole (SMX), bisphenol A (BPA) and diclofenac (DCF), by nitrifying activated sludge as well as whole-cell and extracellular enzyme (laccase) extract of the white-rot fungus Trametes versicolor. Fungal whole-cell culture removed only BPA and DCF but with high efficiencies (>90%) while the mixed nitrifying culture removed all compounds, although by levels …

Protease-Activated Alpha-2-Macroglobulin Can Inhibit Amyloid Formation Via Two Distinct Mechanisms, Amy R. Wyatt, Patrick Constantinescu, Heath Ecroyd, Christopher M. Dobson, Mark R. Wilson, Janet R. Kumita, Justin J. Yerbury

Faculty of Science, Medicine and Health - Papers: part A

α2-Macroglobulin (α2M) is an extracellular chaperone that inhibits amorphous and fibrillar protein aggregation. The reaction of α2M with proteases results in an ‘activated’ conformation, where the proteases become covalently-linked within the interior of a cage-like structure formed by α2M. This study investigates, the effect of activation on the ability of α2M to inhibit amyloid formation by Aβ1–42 and I59T human lysozyme and shows that protease-activated α2M can act via two distinct mechanisms: (i) by trapping proteases that remain able to degrade polypeptide chains and (ii) by a chaperone action that prevents misfolded clients from continuing along the amyloid forming pathway.

Escherichia Coli Single-Stranded Dna-Binding Protein: Nanoesi-Ms Studies Of Salt-Modulated Subunit Exchange And Dna Binding Transactions, Claire E. Mason, Slobodan Jergic, Allen Lo, Yao Wang, Nicholas E. Dixon, Jennifer L. Beck

Faculty of Science, Medicine and Health - Papers: part A

Single-stranded DNA-binding proteins (SSBs) are ubiquitous oligomeric proteins that bind with very high affinity to single-stranded DNA and have a variety of essential roles in DNA metabolism. Nanoelectrospray ionization mass spectrometry (nanoESI-MS) was used to monitor subunit exchange in full-length and truncated forms of the homotetrameric SSB from Escherichia coli. Subunit exchange in the native protein was found to occur slowly over a period of hours, but was significantly more rapid in a truncated variant of SSB from which the eight C-terminal residues were deleted. This effect is proposed to result from C-terminus mediated stabilization of the SSB tetramer, in …

P2x7 Receptor Activation Induces Reactive Oxygen Species Formation In Erythroid Cells, Bin Wang, Ronald Sluyter

Faculty of Science, Medicine and Health - Papers: part A

The presence of P2X7 on erythroid cells is well established, but its physiological role remains unclear. The current study aimed to determine if P2X7 activation induces reactive oxygen species (ROS) formation in murine erythroleukaemia (MEL) cells, a commonly used erythroid cell line. ATP induced ROS formation in a time- and concentration-dependent fashion. The most potent P2X7 agonist, 2′(3′)-O-(4-benzoylbenzoyl)ATP, but not UTP or ADP, also induced ROS formation. The P2X7 antagonist, A-438079, impaired ATP-induced ROS formation. The ROS scavenger, N-acetyl-l-cysteine, and the ROS inhibitor, diphenyleneiodonium, also impaired P2X7-induced ROS formation, but use of enzyme-specific ROS inhibitors failed to identify the intracellular …

Proofreading Exonuclease On A Tether: The Complex Between The E. Coli Dna Polymerase Iii Subunits Α, Ε, Θ And Β Reveals A Highly Flexible Arrangement Of The Proofreading Domain, Kiyoshi Ozawa, Nicholas P. Horan, Andrew Robinson, Hiromasa Yagi, Flynn R. Hill, Slobodan Jergic, Zhi-Qiang Xu, Karin V. Loscha, Nan Li, Moeava Tehei, Aaron J. Oakley, Gottfried Otting, Thomas Huber, Nicholas E. Dixon

Faculty of Science, Medicine and Health - Papers: part A

A complex of the three (αεθ) core subunits and the β2 sliding clamp is responsible for DNA synthesis by Pol III, the Escherichia coli chromosomal DNA replicase. The 1.7 Å crystal structure of a complex between the PHP domain of α (polymerase) and the C-terminal segment of ε (proofreading exonuclease) subunits shows that ε is attached to α at a site far from the polymerase active site. Both α and ε contain clamp-binding motifs (CBMs) that interact simultaneously with β2 in the polymerization mode of DNA replication by Pol III. Strengthening of both CBMs enables isolation of stable αεθ:β2 complexes. …

P2x7 Receptor Activation Induces Reactive Oxygen Species Formation And Cell Death In Murine Eoc13 Microglia, Rachael Bartlett, Justin J. Yerbury, Ronald Sluyter

Faculty of Science, Medicine and Health - Papers: part A

The P2X7 purinergic receptor is a ligand-gated cation channel expressed on leukocytes including microglia. This study aimed to determine if P2X7 activation induces the uptake of organic cations, reactive oxygen species (ROS) formation, and death in the murine microglial EOC13 cell line. Using the murine macrophage J774 cell line as a positive control, RT-PCR, immunoblotting, and immunolabelling established the presence of P2X7 in EOC13 cells. A cytofluorometric assay demonstrated that the P2X7 agonists adenosine-5'-triphosphate (ATP) and 2' (3')-O-(4-benzoylbenzoyl) ATP induced ethidium(+) or YO-PRO-1(2+) uptake into both cell lines. ATP induced ethidium+ uptake into EOC13 cells in a concentration-dependent manner, with …

Extracellular Chaperones Prevent Aβ42-Induced Toxicity In Rat Brains, Roberta Cascella, Simona Conti, Francesca Tatini, Elisa Evangelisti, Tania Scartabelli, Fiorella Casamenti, Mark R. Wilson, Fabrizio Chiti, Cristina Cecchi

Faculty of Science, Medicine and Health - Papers: part A

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by cognitive decline, formation of the extracellular amyloid β (Aβ42) plaques, neuronal and synapse loss, and activated microglia and astrocytes. Extracellular chaperones, which are known to inhibit amyloid fibril formation and promote clearance of misfolded aggregates, have recently been shown to reduce efficiently the toxicity of HypF-N misfolded oligomers to immortalised cell lines, by binding and clustering them into large species. However, the role of extracellular chaperones on Aβ oligomer toxicity remains unclear, with reports often appearing contradictory. In this study we microinjected into the hippocampus of rat brains Aβ42 oligomers …

Inhibition Of Tnf-Α Production In Lps-Activated Thp-1 Monocytic Cells By The Crude Extracts Of Seven Bhutanese Medicinal Plants, Phurpa Wangchuk, Paul A. Keller, Stephen G. Pyne, Malai Taweechotipatr

Faculty of Science, Medicine and Health - Papers: part A

Ethnopharmacological relevance Seven studied medicinal plants; Aconitum laciniatum, Ajania nubigena, Codonopsis bhutanica, Corydalis crispa, Corydalis dubia, Meconopsis simplicifolia and Pleurospermum amabile, are currently used in the Bhutanese Traditional Medicine (BTM) for the management of different types of disorders including the diseases that bore relevance to various inflammatory conditions.

Aims of the study This study aimed to evaluate the inhibition of TNF-α production in LPS-activated THP-1 monocytic cells by the crude extracts of seven selected Bhutanese medicinal plants. It is expected to; (a) generate a scientific basis for their use in the BTM and (b) form a basis for prioritization of …

Chemical Constituents And Biological Activities Of Garcinia Cowa Roxb, Thunwadee Ritthiwigrom, Surat Laphookhieo, Stephen G. Pyne

Faculty of Science, Medicine and Health - Papers: part A

Garcinia cowa is an abundant source of bioactive phytochemicals. Phytochemical investigations of the plant parts indicated that the fruit, twig and stem are the best source of secondary metabolites, providing flavonoids, phloroglucinols and xanthones respectively. Seventyeight of these compounds have been identified from the plant and several have interesting pharmacological activities.

An Evaluation Of Ferrihydrite- And Metsorb™-Dgt Techniques For Measuring Oxyanion Species (As, Se, V, P): Effective Capacity, Competition And Diffusion Coefficients, Helen L. Price, Peter R. Teasdale, Dianne F. Jolley

Faculty of Science, Medicine and Health - Papers: part A

tThis study investigated several knowledge gaps with respect to the diffusive gradients in thin films(DGT) technique for measurement of oxyanions (As(III), As(V), Se(IV), Se(VI), PO43−, and V(V)) usingthe ferrihydrite and MetsorbTMbinding layers. Elution efficiencies for each binding layer were higherwith 1:20 dilutions, as analytical interferences for ICP-MS were minimised. Diffusion coefficients mea-sured by diffusion cell and by DGT time-series experiments were found to agree well and generallyagreed with previously reported values, although a range of diffusion coefficients have been reportedfor inorganic As and Se species. The relative binding affinity for both ferrihydrite and MetsorbTMwasPO43−≈ As(V) > V(V) ≈ As(III) > Se(IV) ≫ …

Stereoselective Synthesis Of Α-Methylenecyclopentenones Via A Diels-Alder/Retro-Diels-Alder Protocol, Weerachai Phutdhawong, Gedsirin Eksinitkun, Stephen G. Pyne, Anthony C. Willis, Waya S. Phutdhawong

Faculty of Science, Medicine and Health - Papers: part A

A new procedure for the stereoselective synthesis of cross-conjugated dienones is reported. This method makes use of the Diels–Alder adduct of anthracene and dimethyl fumarate, a precursor to a spirocyclopent-2-enone anthracene adduct as the key intermediate. The addition of propyllithium or octyllithium to the key intermediate followed by a retro-Diels–Alder reaction furnished α-methylenecyclopentenones bearing a γ-propyl or γ-octyl side chain, respectively, in moderate yields and as single geometric isomers.

Gc/Gc-Ms Analysis, Isolation And Identification Of Bioactive Essential Oil Components From The Bhutanese Medicinal Plant, Pleurospermum Amabile, Phurpa Wangchuk, Paul A. Keller, Stephen G. Pyne, Malai Taweechotipatr, Sumalee Kamchonwongpaisan

Faculty of Science, Medicine and Health - Papers: part A

We have hydrodistilled the essential oil (EO) from the aerial parts of the Bhutanese medicinal plant, Pleurospermum amabile using a Clevenger apparatus and evaluated this EO by GC/GC-MS and NMR analysis followed by testing for bioactivity. The GC-MS analysis identified 52 compounds with (E)-isomyristicin as a major component (32.2%). Repeated purification yielded four compounds; (E)-isomyristicin (1), (E)-isoapiol (2), methyl eugenol (3) and (E)-isoelemicin (4). Compound 2 and the mother EO showed the best antiplasmodial activity against the Plasmodium falciparum strains, TM4/8.2 (chloroquine and antifolate sensitive) and K1CB1 (multidrug resistant). They exhibited mild antibacterial activity against Bacillus subtilis. None of the …

Parviflorals A-F, Trinorcadalenes And Bis-Trinorcadalenes From The Roots Of Decaschistia Parviflora, Nikhom Wongsa, Somdej Kanokmedhakul, Kwanjai Kanokmedhakul, Palangpon Kongsaeree, Samran Prabpai, Stephen G. Pyne

Faculty of Science, Medicine and Health - Papers: part A

Trinorcadalenes, parviflorals A and B (1 and 2), and four bis-trinorcadalenes, parviflorals C–F (3–6), together with the known trinorcadalenes, syriacusins A (7) and C (8), scopoletin (9) and stigmasterol were isolated from roots of Decaschistia parviflora. Their structures were established by spectroscopic techniques. The CD spectra of the bis-trinorcadalenes (3–6) established their absolute configurations at the binaphthyl axis. Further, structure 6 was confirmed by a single-crystal X-ray crystallographic analysis. Compounds 2 and 6 showed antimalarial activity against Plasmodium falciparum with IC50 values of 11.45 and 6.85 μM, respectively. Compounds 1, 5, 7 and 8 also exhibited weak antifungal activity against …

Bioassays For Anticancer Activities, Janice Mccauley, Ana Zivanovic, Danielle Skropeta

Faculty of Science, Medicine and Health - Papers: part A

The MTT/MTS in vitro cell proliferation assay is one of the most widely used assays for evaluating preliminary anticancer activity of both synthetic derivatives and natural products and natural product extracts. The highly reliable, colorimetric based assay is readily performed on a wide range of cell lines. This assay gives an indication of whole cell cytotoxicity; however, to determine the exact molecular target further assays need to be performed. Of these, kinase inhibition assays are also one of the most widespread enzyme inhibition screening assays performed. Kinases are enzymes that play a key role in a number of physiological processes …