A5082018013- Porphyrin and Phthalocyanine Chemistry
- Oxidative Organic Chemistry Reactions
- Dyeing and Modifying Textile Fibers
- Metal complexes synthesis and properties
- Parkinson's Disease Mechanisms and Treatments
- Metal-Catalyzed Oxygenation Mechanisms
- Supramolecular Chemistry and Complexes
- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Advancements in Transdermal Drug Delivery
- Photosynthetic Processes and Mechanisms
- Lipid Membrane Structure and Behavior
- Sphingolipid Metabolism and Signaling
- Chemical Synthesis and Reactions
- Amino Acid Enzymes and Metabolism
- Molecular Junctions and Nanostructures
- Synthesis of Organic Compounds
- X-ray Diffraction in Crystallography
- Free Radicals and Antioxidants
- Electron Spin Resonance Studies
- Mechanisms of cancer metastasis
- Computational Drug Discovery Methods
- Chemical Synthesis and Analysis
- Nuclear Receptors and Signaling
- Neurological diseases and metabolism
Northumbria University
2014-2023
North Carolina State University
2017
In-Q-Tel
2015
Cumbria Northumberland Tyne and Wear NHS Foundation Trust
2015
Applied Sciences (United States)
1997-2012
University of Warwick
1999
University of Manchester
1999
CEA LETI
1999
Laboratoire de Chimie Organique
1997
Centre National de la Recherche Scientifique
1996-1997
While the etiology of non-familial Parkinson's disease (PD) remains unclear, there is evidence that increased levels tissue iron may be a contributing factor. Moreover, exposure to some environmental toxicants considered an additional risk Therefore, brain-targeted chelators are interest as antidotes for poisoning with dopaminergic toxicants, and potential treatment PD. We, therefore, designed series small molecules high affinity ferric containing structural elements allow their transport...
Brain iron accumulation has been associated with inciting the generation of oxidative stress in a host chronic neurological diseases, including Parkinson's disease. Using catecholaminergic neurotoxin 6-hydroxydopamine to lesion cellular dopaminergic pathways as model disease culture, selection 1-hydroxypyridin-2-one (1,2-HOPO) metal chelators were synthesized and their neuroprotective properties compared 3-hydroxypyridin-4-one; deferiprone (3,4-HOPO; DFP). Protection against 6-OHDA insult by...
Several novel chelators based on 1-hydroxy-2(1H)-pyridinone coordinating groups decorating a triaza macrocyclic backbone scaffold were synthesised as potential powerful Fe3 + capable of competing with bacterial siderophores. In particular, chloromethyl derivative exploiting protective group for this family was developed. These are the first examples hexadentate to be shown have biostatic activity against range pathogenic bacteria. Their efficacy agents assessed revealing that minor...
Summary The anticancer activity of a series novel synthesized, hydroxypyridone-based metal chelators (analogues L- mimosine) was evaluated in an vitro model melanoma consisting malignant (A375), non-melanoma epidermoid carcinoma (A431) and immortalized non-malignant keratinocyte (HaCaT) cells. More specifically, we have demonstrated that the enantiomer methylated analogue mimosine (compound 22) can exert potent effect A375 cells when compared to either A431 or HaCaT Moreover, this has...
D. Tétard, A. Rabion, J. Verlhac and Guilhem, Chem. Soc., Commun., 1995, 531 DOI: 10.1039/C39950000531
Di-µ-oxo dimanganese(III/IV) complexes are efficient catalysts for H2O2 disproportionation in neutral aqueous medium; the activity can be correlated to electron density on metal and accessibility of catalytic site.
The electrochemistry of a benzylic amide [2]catenane was investigated and compared to that its topologically trivial components. redox behavior both the catenane uninterlocked macrocycle can be largely understood in terms smaller molecular fragments simple orbital considerations show electroactivity CO groups is split into two sets quasi-degenerate potentials separated by substantial gap. A fast intermolecular reaction follows reduction fragments, consistent with corresponding dimers...
Abstract Ubiquitin proteasome system (UPS) impairment, excessive cellular oxidative stress, and iron dyshomeostasis are key to substantia nigra dopaminergic neuronal degeneration in Parkinson's disease (PD); however, a link between these features remains unconfirmed. Using the inhibitor lactacystin we confirm that nigral injury via UPS impairment disrupts homeostasis, turn increasing stress promoting protein aggregation. We demonstrate neuroprotective potential of two novel...
We report that novel 1-hydroxypyazin-2(1 H )-ones show comparable neuroprotective effects to related iron chelators in a cell culture model of Parkinson's disease, despite significant differences their physicochemical properties.
Melanoma is an aggressive and highly metastatic type of skin cancer where the design new therapies utmost importance for clinical management disease. Thus, we have aimed to investigate mode action by which a novel methylated analogue L-Mimosine (e.g., L-SK-4) exerts its therapeutic potency in vitro model malignant melanoma. Cytotoxicity was assessed Alamar Blue assay, oxidative stress commercially available kits, ROS generation, caspase 3/7 activation mitochondrial membrane depolarisation...
Abstract Tin hydride reduction of ω-iodo-polyoxaalkyl acrylates 1 using syringe pump addition both reactants to a solution AIBN in benzene at 80°C afforded the corresponding cyclic polyethers excellent yields.
Iron is an essential micronutrient due to its involvement in many cellular processes including DNA replication and OXPHOS. Tumors overexpress iron metabolism linked proteins which allow for accumulation driving high levels of proliferation. Our group has designed novel chelator SK4 targets cancer’s “iron addiction.” comprises two key moieties: chelation moiety responsible cytotoxicity amino acid allows entry through transporter LAT1. We selected LAT1 as a route it commonly overexpressed...
Anti-cancer therapy by iron chelation has been shown to inhibit many cellular processes including DNA replication, mitochondrial metabolism and oncogenic signalling pathways (e.g., EGFR). Iron chelator SK4 represents a double pronged approach towards treating cancer. enters through LAT1, commonly overexpressed amino acid transporter in tumours, thus targeting addiction LAT1 overexpression. The aim of this study was characterise the mode action proteomics, metabolomics, lipidomics seahorse...
Two analogues of tolcapone where the nitrocatechol group has been replaced by a 1-hydroxy-2(1H)-pyridinone have designed and synthesised. These compounds are expected to dual mode action both beneficial against Parkinson's disease: they be inhibitors catechol O-methyl transferase, which contribute reduction dopamine in brain, protect neurons oxidative damage. To assess whether these worthy biological assessment demonstrate effects, measurement their pKa stability constants for Fe(III),...