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Articles 31 - 36 of 36

Full-Text Articles in Organic Chemicals

Β-Lactam Estrogen Receptor Antagonists And A Dual-Targeting Estrogen Receptor/Tubulin Ligand, Niamh O'Boyle, Jade K. Pollock, Miriam Carr, Andrew Js Knox, Seema M. Nathwani, Shu Wang, Laura Caboni, Daniela M. Zisterer, Mary Meegan Jan 2014

Β-Lactam Estrogen Receptor Antagonists And A Dual-Targeting Estrogen Receptor/Tubulin Ligand, Niamh O'Boyle, Jade K. Pollock, Miriam Carr, Andrew Js Knox, Seema M. Nathwani, Shu Wang, Laura Caboni, Daniela M. Zisterer, Mary Meegan

Articles

Twelve novel β-lactams were synthesised and their antiproliferative effects and binding affinity for the predominant isoforms of the estrogen receptor (ER), ERα and ERβ, were determined. β-Lactams 23 and 26 had the strongest binding affinities for ERα (IC50 values: 40 and 8 nM respectively) and ERβ (IC50 values: 19 and 15 nM). β-Lactam 26 was the most potent in antiproliferative assays using MCF-7 breast cancer cells, and further biochemical analysis showed that it caused accumulation of cells in G2/M phase (mitotic blockade) and depolymerisation of tubulin in MCF-7 cells. Compound 26 also induced apoptosis and downregulation …


Kinetics And Mechanism Of S-Nitrosation And Oxidation Of Cysteamine By Peroxynitrite, Wilbes Mbiya Sep 2013

Kinetics And Mechanism Of S-Nitrosation And Oxidation Of Cysteamine By Peroxynitrite, Wilbes Mbiya

Dissertations and Theses

Cysteamine (CA), which is an aminothiol drug medically known as Cystagon® was studied in this thesis. Cysteamine was reacted with a binary toxin called peroxynitrite (PN) which is assembled spontaneously whenever nitric oxide and superoxide are produced together and the decomposition of peroxyinitrite was monitored. PN was able to nitrosate CA in highly acidic medium and excess CA to form S-nitrosocysteamine (CANO) in a 1:1 with the formation of one mole of CANO from one mole of ONOOH. In excess oxidant (PN) the following 1:2 stoichiometric ratio was obtained; ONOO- + 2CA → CA-CA + NO2- + H …


Analogues Of The Epoxy Resin Monomer Diglycidyl Ether Of Bisphenol F: Effects On Contact Allergenic Potency And Cytotoxicity, Niamh O'Boyle, Tamara Delaine, Kristina Luthman, Andreas Natsch, Ann-Therese Karlberg Jan 2012

Analogues Of The Epoxy Resin Monomer Diglycidyl Ether Of Bisphenol F: Effects On Contact Allergenic Potency And Cytotoxicity, Niamh O'Boyle, Tamara Delaine, Kristina Luthman, Andreas Natsch, Ann-Therese Karlberg

Articles

Diglycidyl ethers of bisphenol A (DGEBA) and bisphenol F (DGEBF) are widely used as components in epoxy resin thermosetting products. They are known to cause occupational and non-occupational allergic contact dermatitis. The aim of this study is to investigate analogues of DGEBF with regard to contact allergy and cytotoxicity. A comprehensive knowledge of the structural features that contribute to the allergenic and cytotoxic effects of DGEBF will guide the development of future novel epoxy resin systems with reduced health hazards for those coming into contact with them. It was found that the allergenic effects of DGEBF were dependent on its …


Life As A Swimmer, Danielle N. Coville Aug 2011

Life As A Swimmer, Danielle N. Coville

Chemistry and Biochemistry

No abstract provided.


Synthesis, Biochemical And Molecular Modelling Studies Of Antiproliferative Azetidinones Causing Microtubule Disruption And Mitotic Catastrophe, Niamh O'Boyle, Miriam Carr, Lisa M. Greene, Niall O. Keely, Andrew Js Knox, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan Jan 2011

Synthesis, Biochemical And Molecular Modelling Studies Of Antiproliferative Azetidinones Causing Microtubule Disruption And Mitotic Catastrophe, Niamh O'Boyle, Miriam Carr, Lisa M. Greene, Niall O. Keely, Andrew Js Knox, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan

Articles

The structure-activity relationships of antiproliferative β-lactams, focusing on modifications at the 4-position of the β-lactam ring, is described. Synthesis of this series of compounds was achieved utilizing the Staudinger and Reformatsky reactions. The antiproliferative activity was assessed in MCF-7 cells, where the 4-(4-ethoxy)phenyl substituted compound 26 displayed the most potent activity with an IC50 value of 0.22 μM. The mechanism of action was demonstrated to be by inhibition of tubulin. Cell exposure to combretastatin A-4 and 26 led to arrest of MCF-7 cells in the G2/M phase of the cell cycle and induction of apoptosis. Additionally, mitotic catastrophe for …


Lead Identification Of Β-Lactam And Related Imine Inhibitors Of The Molecular Caperone Heat Shock Protein 90, Niamh O'Boyle, Andrew Js Knox, Trevor P. Price, D. Clive Williams, Daniela M. Zisterer, David G. Lloyd, Mary J. Meegan Jan 2011

Lead Identification Of Β-Lactam And Related Imine Inhibitors Of The Molecular Caperone Heat Shock Protein 90, Niamh O'Boyle, Andrew Js Knox, Trevor P. Price, D. Clive Williams, Daniela M. Zisterer, David G. Lloyd, Mary J. Meegan

Articles

Heat shock protein 90 is an emerging target for oncology therapeutics. Inhibitors of this molecular chaperone, which is responsible for the maintenance of a number of oncogenic proteins, have shown promise in clinical trials and represent a new and exciting area in the treatment of cancer. Heat shock protein 90 inhibitors have huge structural diversity, and here we present the identification of inhibitors based on β-lactam and imine templates. β-Lactam 5 and imines 12 and 18 exhibit binding to heat shock protein 90-α with IC50 values of 5.6 μM, 14.5 μM and 22.1 μM respectively. The binding affinity displayed …