title: Aryl azoles with neuroprotective activity--parallel synthesis and attempts at target identification.
abstract: A parallel synthesis of aryl azoles with neuroprotective activity is described. All compounds obtained were evaluated in an in vitro assay using a NMDA toxicity paradigm showing a neuroprotective activity between 15% and 40%. The potential biological target of the active compounds was investigated by extensive literature searches based around similar scaffolds with reported neuroprotective activity. The most interesting molecules active in the NMDA toxicity assay (3a and 2g) showed moderate but significant activity in the inhibition of the Site 2 Sodium Channel binding assay at 10 microM. To confirm our hypothesis compounds 3a, c, f and 2g were tested in the Veratridine assay which is one of the excitotoxicity assays of relevance to NaV channels. The compounds tested showed an activity between 40% and 70%. The identification of neuroprotective small molecules and the identification of NaV channels as the potential site of action were the most important goals of this work.
authors.affiliation: Siena Biotech S.p.A., via Fiorentina 1, 53100 Siena, Italy. gcocconcelli@sienabiotech.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cocconcelli
authors.forename: Enrica
authors.initials: E
authors.lastname: Diodato
authors.forename: Andrea
authors.initials: A
authors.lastname: Caricasole
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gaviraghi
authors.forename: Eva
authors.initials: E
authors.lastname: Genesio
authors.forename: Chiara
authors.initials: C
authors.lastname: Ghiron
authors.forename: Letizia
authors.initials: L
authors.lastname: Magnoni
authors.forename: Elena
authors.initials: E
authors.lastname: Pecchioli
authors.forename: Pier Vincenzo
authors.initials: PV
authors.lastname: Plazzi
authors.forename: Georg C
authors.initials: GC
authors.lastname: Terstappen
mesh_terms: D000818:Animals; D001393:Azoles / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D016202:N-Methylaspartate / Q000633:toxicity; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000138:chemical synthesis / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects
chemical_list: D001393:Azoles; D018696:Neuroprotective Agents; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D016202:N-Methylaspartate