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dc.contributor.authorJoubert, Jacques
dc.contributor.authorMalan, Sarel Francois
dc.contributor.authorVan Dyk, Sandra
dc.contributor.authorGreen, I. van R.
dc.date.accessioned2012-10-04T07:10:24Z
dc.date.available2012-10-04T07:10:24Z
dc.date.issued2011
dc.identifier.citationJoubert, J. et al. 2011. Synthesis, evaluation and application of polycyclic fluorescent analogues as N-methyl-D-aspartate receptor and voltage gated calcium channel ligands. European journal of medicinal chemistry, 46(10):5010-5020. [http://www.journals.elsevier.com/european-journal-of-medicinal-chemistry/]en_US
dc.identifier.issn0223-5234
dc.identifier.issn1768-3254 (Online)
dc.identifier.urihttp://hdl.handle.net/10394/7438
dc.descriptionPublished under the auspices of the French Société de Chimie Thérapeutique (SCT)en_US
dc.description.abstractA series of polycyclic fluorescent ligands were synthesised and evaluated in murine striatal synaptoneurosomes for N-methyl-D-aspartate receptor (NMDAR) mediated calcium flux inhibition and inhibition of calcium influx through voltage gated calcium channels (VGCC). Amantadine (a) and N-(1-adamantyl)-1,3-propanediamine (c) substituted with 1-cyanoisoindole (3), indazole (5), dinitrobenzene (7, 8), dansyl (9, 10) and coumarin (11) moieties showed moderate to high inhibition of the NMDAR. A high degree of VGCC inhibitionwas observed for the cyanoisoindole compounds (3, 4) the dansyl compounds (9, 10) and the coumarin compound (12). Fluorophores conjugated to hydroxy-4-aza-8-oxoheptacyclotetradecane (13, 14) did not exhibit any significant VGCC inhibition, but the indazole conjugate (14) showed promising NMDAR activity. Dose response curves were calculated for selected NMDAR inhibitors (8e11) and N-[3-(1-adamantylamino)propyl]-5-dimethylaminonaphthalene-1-sulfonamide (10) exhibited the highest activity of the novel compounds. Compound 10 was further used as a fluorescent NMDAR ligand in a fluorescent competition assay utilizing MK-801, NGP1-01 and amantadine as known NMDAR inhibitors to demonstrate the possible applications of the novel fluorescent compounds. These small molecule fluorescent ligands can be considered as possible pharmacological tools in assay development and/or other investigations in the study of neurodegeneration.en_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.subjectPolycyclicen_US
dc.subjectamantadineen_US
dc.subjectNMDARen_US
dc.subjectcalcium channelsen_US
dc.subjectfluorescent ligandsen_US
dc.titleSynthesis, evaluation and application of polycyclic fluorescent analogues as N-methyl-D-aspartate receptor and voltage gated calcium channel ligandsen_US
dc.typeArticleen_US


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