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Auranofin

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https://www.readbyqxmd.com/read/29223747/an-automated-high-throughput-system-for-phenotypic-screening-of-chemical-libraries-on-c-elegans-and-parasitic-nematodes
#1
Frederick A Partridge, Anwen E Brown, Steven D Buckingham, Nicky J Willis, Graham M Wynne, Ruth Forman, Kathryn J Else, Alison A Morrison, Jacqueline B Matthews, Angela J Russell, David A Lomas, David B Sattelle
Parasitic nematodes infect hundreds of millions of people and farmed livestock. Further, plant parasitic nematodes result in major crop damage. The pipeline of therapeutic compounds is limited and parasite resistance to the existing anthelmintic compounds is a global threat. We have developed an INVertebrate Automated Phenotyping Platform (INVAPP) for high-throughput, plate-based chemical screening, and an algorithm (Paragon) which allows screening for compounds that have an effect on motility and development of parasitic worms...
December 2, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29221187/selection-and-characterization-of-a-human-ovarian-cancer-cell-line-resistant-to-auranofin
#2
Ida Landini, Andrea Lapucci, Alessandro Pratesi, Lara Massai, Cristina Napoli, Gabriele Perrone, Pamela Pinzani, Luigi Messori, Enrico Mini, Stefania Nobili
The anti-arthritic drug auranofin exerts also potent antitumour activity in in vitro and in vivo models, whose mechanisms are not yet well defined. From an auranofin-sensitive human ovarian cancer cell line A2780, a highly resistant (>20-fold) subline (A2780/AF-R) was developed and characterized. Marked reduction of gold accumulation occurred in auranofin-resistant A2780 cells. Also, moderately higher thioredoxin reductase activity in A2780/AF-R cells was observed while no changes in intracellular glutathione content occurred...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29194002/auranofin-a-thioredoxin-reductase-inhibitor-causes-platelet-death-through-calcium-overload
#3
Matthew T Harper
Platelets are central to normal hemostasis and must be tightly controlled to prevent thrombosis. However, drug treatments that also affect platelets could lead to unwanted side effects on hemostasis or thrombosis. In this study, the effect of auranofin on platelets was tested. Auranofin, a gold-based thioredoxin reductase (TRXR) inhibitor, has been previously used in arthritis. Recently, auranofin and other inhibitors of the thioredoxin system have been proposed as novel anti-cancer therapies. TRXR is an important part of the antioxidant defenses in many cells that maintain intracellular proteins in their reduced state...
December 1, 2017: Platelets
https://www.readbyqxmd.com/read/29077771/correction-correction-auranofin-inhibits-retinal-pigment-epithelium-cell-survival-through-reactive-oxygen-species-dependent-epidermal-growth-factor-receptor-mitogen-activated-protein-kinase-signaling-pathway
#4
https://www.readbyqxmd.com/read/29065820/recent-advances-in-antabuse-disulfiram-the-importance-of-its-metal-binding-ability-to-its-anticancer-activity
#5
Maricela Viola-Rhenals, Kush Rohit Patel, Laura Jaimes-Santamaria, Guojun Wu, Jinbao Liu, Q Ping Dou
Disulfiram (DSF, also called tetraethylthiuram disulphide), a disulfide derivative of N,N-diethyldithiocarbamate (DEDTC), is an antialcoholism drug that is currently being repurposed as a promising anticancer drug. DSF has been investigated in many studies, including in vitro, in vivo, preclinical and clinical. Various mechanisms have been proposed to be responsible for the cytotoxic effect of DSF on cancer cells. DSF is a pro-drug which is converted to its metabolite DEDTC in human body. A complex of DEDTC with a metal ion [usually Cu(II) or Zn(II)] could be responsible for the anticancer activity of DSF in breast, prostate, glioblastoma, lung, melanoma, cervical, colorectal cancers as well as myeloma and leukemia...
October 23, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29057040/auranofin-et3paucl-and-et3paui-are-highly-cytotoxic-on-colorectal-cancer-cells-a-chemical-and-biological-study
#6
Tiziano Marzo, Damiano Cirri, Chiara Gabbiani, Tania Gamberi, Francesca Magherini, Alessandro Pratesi, Annalisa Guerri, Tarita Biver, Francesca Binacchi, Matteo Stefanini, Annarosa Arcangeli, Luigi Messori
The solution behavior of auranofin, Et3PAuCl  and Et3PAuI, as well as their interactions with hen egg white lysozyme, single strand oligonucleotide, and ds-DNA were comparatively analyzed through NMR spectroscopy, ESI-MS, ethidium bromide displacement, DNA melting and viscometric tests. The cytotoxic effects toward representative colorectal cancer cell lines were found to be strong and similar in the three cases and a good correlation could be established between the cytotoxicity and the ability to inhibit thioredoxin reductase; remarkably, in vivo acute toxicity experiments for Et3PAuI confirmed that, similarly to auranofin, this drug is well tolerated in a murine model...
October 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29039082/metal-based-proteasomal-deubiquitinase-inhibitors-as-potential-anticancer-agents
#7
Xin Chen, Qianqian Yang, Lu Xiao, Daolin Tang, Q Ping Dou, Jinbao Liu
Deubiquitinases (DUBs) play an important role in protein quality control in eukaryotic cells due to their ability to specifically remove ubiquitin from substrate proteins. Therefore, recent findings have focused on the relevance of DUBs to cancer development, and pharmacological intervention on these enzymes has become a promising strategy for cancer therapy. In particular, several DUBs are physically and/or functionally associated with the proteasome and are attractive targets for the development of novel anticancer drugs...
October 16, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28984321/the-cytotoxicity-and-mechanism-of-action-of-new-multinuclear-scaffold-au-iii-pd-ii-pincer-complexes-containing-a-bis-diphenylphosphino-ferrocene-non-ferrocene-ligand
#8
Leila Tabrizi, Hossein Chiniforoshan
New multinuclear gold(iii), palladium(ii) pincer complexes containing bis(diphenylphosphino) ferrocene/non-ferrocene ligands of formula [(L)Au(μ(2)-η(2)-CS3)Pd(dppf)](PF6)2, 1, and [(L)Au(μ(2)-η(2)-CS3)Pd(dppe)](PF6)2, 2 (HL = 5-methoxy-1,3-bis (1-methyl-1H-benzo[d]imidazol-2-yl)benzene, dppf = 1,1'-bis(diphenylphosphino)ferrocene, and dppe = bis(diphenylphosphino)ethane) have been synthesized and fully characterized. Both complexes are more cytotoxic to a number of human cancer cell lines than cisplatin...
October 24, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28981107/targeting-redox-homeostasis-in-rhabdomyosarcoma-cells-gsh-depleting-agents-enhance-auranofin-induced-cell-death
#9
Karoline Johanna Habermann, Leon Grünewald, Sjoerd van Wijk, Simone Fulda
Rhabdomyosarcoma (RMS) cells have recently been reported to be sensitive to oxidative stress. Therefore, we investigated whether concomitant inhibition of the two main antioxidant defense pathways, that is, the thioredoxin (TRX) and the glutathione (GSH) systems, presents a new strategy to trigger cell death in RMS. In this study, we discover that GSH-depleting agents, i.e. γ-glutamylcysteine synthetase inhibitor, buthionine sulfoximine (BSO) or the cystine/glutamate antiporter inhibitor erastin (ERA), synergize with thioredoxin reductase (TrxR) inhibitor auranofin (AUR) to induce cell death in RMS cells...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28947276/selective-inhibition-of-endogenous-antioxidants-with-auranofin-causes-mitochondrial-oxidative-stress-which-can-be-countered-by-selenium-supplementation
#10
Filip Radenkovic, Olivia Holland, Jessica J Vanderlelie, Anthony V Perkins
Auranofin is a thiol-reactive gold (I)-containing compound with potential asa chemotherapeutic. Auranofin has the capacity to selectively inhibit endogenous antioxidant enzymes thioredoxin reductase (TrxR) and glutathione peroxidase (GPx), resulting in oxidative stress and the initiation of a pro-apoptotic cascade. The effect of Auranofin exposure on TrxR and GPx, and the potential for cellular protection through selenium supplementation was examined in the non-cancerous human cell line Swan-71. Auranofin exposure resulted in a concentration dependent differential inhibition of selenoprotein antioxidants...
September 22, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28937773/probing-the-hiv-1-ncp7-nucleocapsid-protein-with-site-specific-gold-i-phosphine-complexes
#11
Raphael E F de Paiva, Zhifeng Du, Erica J Peterson, Pedro P Corbi, Nicholas P Farrell
In this work, we examined a series of thiophilic Au(I) compounds based on [Au(L)(PR3)] (L = Cl(-), 4-dimethylaminopyridine (dmap); R= ethyl (Et), cyclohexyl (Cy)) for chemoselective auration of the C-terminal HIV nucleocapsid protein NCp7 F2 and the "full" HIV NCp7 (NC, zinc finger (ZnF)) as probes of nucleocapsid topography. The choice of phosphine allowed electronic and steric effects to be considered. The use of the heterocycle "leaving group" allowed us to study the effect of possible π-stacking with the essential tryptophan residue of NC on the reactivity and selectivity, mimicking the naturally occurring interaction between the zinc finger and nucleic acids...
September 22, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28913818/a-spectroscopic-study-of-interaction-of-auricyanide-with-n-acetylcysteine
#12
Syed G T Kazimi, Mohammad S Iqbal, C Frank Shaw
Interaction of auricyanide, an important metabolite of anti-arthritic gold-based drug auranofin, was studied in vitro with a pharmacologically active ligand n-acetylcysteine with a view to understand reactivity of gold in vivo. Formation of reduction product aurocyanide occurred through mono- and di-n-acetylcysteine-substituted intermediates. The product and intermediates were identified and monitored spectrophotometrically and by electrospray ionization mass spectrometry. This study suggests successive substitution with n-acetylcysteine through trans effect...
September 14, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28910741/drug-susceptibility-testing-in-microaerophilic-parasites-cysteine-strongly-affects-the-effectivities-of-metronidazole-and-auranofin-a-novel-and-promising-antimicrobial
#13
David Leitsch
The microaerophilic parasites Entamoeba histolytica, Trichomonas vaginalis, and Giardia lamblia annually cause hundreds of millions of human infections which are treated with antiparasitic drugs. Metronidazole is the most often prescribed drug but also other drugs are in use, and novel drugs with improved characteristics are constantly being developed. One of these novel drugs is auranofin, originally an antirheumatic which has been relabelled for the treatment of parasitic infections. Drug effectivity is arguably the most important criterion for its applicability and is commonly assessed in susceptibility assays using in vitro cultures of a given pathogen...
September 5, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28906491/cystatin-sn-inhibits-auranofin-induced-cell-death-by-autophagic-induction-and-ros-regulation-via-glutathione-reductase-activity-in-colorectal-cancer
#14
Byung Moo Oh, Seon-Jin Lee, Hee Jun Cho, Yun Sun Park, Jong-Tae Kim, Suk Ran Yoon, Sang Chul Lee, Jong-Seok Lim, Bo-Yeon Kim, Yong-Kyung Choe, Hee Gu Lee
This corrects the article DOI: 10.1038/cddis.2017.100.
September 14, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28904004/jadomycins-inhibit-type-ii-topoisomerases-and-promote-dna-damage-and-apoptosis-in-multidrug-resistant-triple-negative-breast-cancer-cells
#15
Steven R Hall, Jay Toulany, Leah G Bennett, Camilo F Martinez-Farina, Andrew W Robertson, David L Jakeman, Kerry B Goralski
Jadomycins are natural products that kill drug-sensitive and multidrug-resistant (MDR) breast cancer cells. To date, the cytotoxic activity of jadomycins has never been tested in MDR breast cancer cells that are also triple negative. Additionally, there is only a rudimentary understanding of how jadomycins cause cancer cell death, which includes the induction of intracellular reactive oxygen species (ROS). We first created a paclitaxel-resistant, triple-negative breast cancer cell line [paclitaxel-resistant MDA-MB-231 breast cancer cells (231-TXL)] from drug-sensitive control MDA-MB-231 cells (231-CON)...
November 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28840394/lipophilic-gold-i-complexes-with-1-3-4-oxadiazol-2-thione-or-1-3-thiazolidine-2-thione-moieties-synthesis-and-their-cytotoxic-and-antimicrobial-activities
#16
Angelina Maria de Almeida, Bruno Assis de Oliveira, Pedro Pôssa de Castro, Camille Carvalho de Mendonça, Ricardo Andrade Furtado, Heloiza Diniz Nicolella, Vânia Lúcia da Silva, Cláudio Galuppo Diniz, Denise Crispim Tavares, Heveline Silva, Mauro Vieira de Almeida
Novel lipophilic gold(I) complexes containing 1,3,4-oxadiazol-2-thione or 1,3-thiazolidine-2-thione derivatives were synthesized and characterized by IR, high resolution mass spectrometry, and (1)H, (13)C (31)P NMR. The cytotoxicity of the compounds was evaluated considering cisplatin and/or auranofin as reference in different tumor cell lines: colon cancer (CT26WT), metastatic skin melanoma (B16F10), breast adenocarcinoma (MCF-7), cervical carcinoma (HeLa), glioblastoma (M059 J). Normal human lung fibroblasts (GM07492-A) and kidney normal cell (BHK-21) were also evaluated...
August 24, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28768237/annexin-a5-suppresses-cyclooxygenase-2-expression-by-downregulating-the-protein-kinase-c-%C3%AE-nuclear-factor-%C3%AE%C2%BAb-signaling-pathway-in-prostatfe-cancer-cells
#17
Hyoung-Seok Baek, Nahee Park, Yeo-Jung Kwon, Dong-Jin Ye, Sangyun Shin, Young-Jin Chun
Annexin A5 (ANXA5) is a member of the annexin protein family. Previous studies have shown that ANXA5 is involved in anti-inflammation and cell death. However, the detailed mechanism of the role of ANXA5 in cancer cells is not well understood. In this study, we investigated the inhibitory effect of ANXA5 on cyclooxygenase-2 (COX-2) in prostate cancer cells. Expression of COX-2 induced by TNF-α was inhibited by overexpression of ANXA5 and inhibition of COX-2 expression by auranofin, which could induce ANXA5 expression, was restored by ANXA5 knockdown...
July 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28765909/attenuation-of-muc4-potentiates-the-anticancer-activity-of-auranofin-via-regulation-of-the-her2-akt-foxo3-pathway-in-ovarian-cancer-cells
#18
Jun Sang Bae, Jongsung Lee, Yoonkook Park, Kyungmoon Park, Jung Ryul Kim, Dong Hyu Cho, Kyu Yun Jang, See-Hyoung Park
Previously, we reported that auranofin induces apoptosis in SKOV3 cells via regulation of the IKKβ/FOXO3 pathway. In the present study, we reveal that the anticancer activity of auranofin in SKOV3 cells could be enhanced by the attenuation of MUC4 through the regulation of the Her2/Akt/FOXO3 pathway. Compared to the control-siRNA, siRNA transfection against MUC4 into SKOV3 cells accelerated the protein degradation of Her2. Under the same conditions, the expression level of phosphorylated Akt was also downregulated leading to an increase of FOXO3 in the nucleus...
July 28, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28716566/combatting-bacterial-persister-cell-infections-by-auranofin
#19
EDITORIAL
Babak Asghari, Hamid Reza Sadeghi, Hamzeh Mazaherylaghab
No abstract text is available yet for this article.
July 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28684416/thioredoxin-reductase-1-and-nadph-directly-protect-protein-tyrosine-phosphatase-1b-from-inactivation-during-h2o2-exposure
#20
COMPARATIVE STUDY
Markus Dagnell, Paul E Pace, Qing Cheng, Jeroen Frijhoff, Arne Östman, Elias S J Arnér, Mark B Hampton, Christine C Winterbourn
Regulation of growth factor signaling involves reversible inactivation of protein tyrosine phosphatases (PTPs) through the oxidation and reduction of their active site cysteine. However, there is limited mechanistic understanding of these redox events and their co-ordination in the presence of cellular antioxidant networks. Here we investigated interactions between PTP1B and the peroxiredoxin 2 (Prx2)/thioredoxin 1 (Trx1)/thioredoxin reductase 1 (TrxR1) network. We found that Prx2 becomes oxidized in PDGF-treated fibroblasts, but only when TrxR1 has first been inhibited...
September 1, 2017: Journal of Biological Chemistry
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