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1.
Bioorg Med Chem Lett ; 29(7): 929-932, 2019 04 01.
Article in English | MEDLINE | ID: mdl-30773432

ABSTRACT

In the course of a programme aimed at identifying Nurr1/NOT agonists for potential treatment of Parkinson's disease, a few hits from high throughput screening were identified and characterized. A combined optimization pointed to a very narrow and stringent structure activity relationship. A comprehensive program of optimization led to a potent and safe candidate drug displaying neuroprotective and anti-inflammatory activity in several in vitro and in vivo models.


Subject(s)
Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/pharmacology , Nuclear Receptor Subfamily 4, Group A, Member 2/metabolism , Parkinson Disease/drug therapy , Animals , Cell Line , Cricetinae , Drug Discovery , Gene Expression Regulation/drug effects , Homeodomain Proteins/metabolism , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Mice , Microglia/drug effects , Molecular Structure , Neurons/drug effects , Nuclear Receptor Subfamily 4, Group A, Member 2/genetics , Rats , Retinoid X Receptors/genetics , Retinoid X Receptors/metabolism
2.
J Magn Reson ; 270: 147-156, 2016 09.
Article in English | MEDLINE | ID: mdl-27479038

ABSTRACT

In vivo electron paramagnetic resonance (EPR) imaging and spectroscopy are non-invasive technologies used to specifically detect and quantify paramagnetic species. However, the relative instability of spin probes such as triarylmethyl radicals limits their application to conduct oxygen quantification and mapping. In this study we encapsulated tetrathiatriarylmethyl radical (TAM; known as "Finland" probe) in Pluronic F-127 hydrogel (PF-127) in order to limit its degradation and evaluate its in vitro and in vivo EPR properties as a function of oxygen. Our results show that the EPR signal of encapsulated TAM in PF-127 hydrogel is similar to the one in solution. Although it is less sensitive to oxygen, it is suitable for oximetry. We also demonstrated that the incorporation of TAM in PF-127 hydrogel leads to an improved in vivo EPR stability of the radical under anesthesia. This new formulation enables high quality EPR imaging and oximetry and paves the way for the application of TAM radical-based probes in various biomedical fields.


Subject(s)
Electron Spin Resonance Spectroscopy , Hydrogels , Poloxamer/chemistry , Free Radicals , Oximetry , Oxygen
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