title: Synthesis and evaluation of fluorescent heterocyclic aminoadamantanes as multifunctional neuroprotective agents.
abstract: A series of fluorescent heterocyclic adamantane amines were synthesised with the goal to develop novel fluorescent ligands for neurological assay development. These derivatives demonstrated multifunctional neuroprotective activity through inhibition of the N-methyl-d-aspartate receptor/ion channel, calcium channels and the enzyme nitric oxide synthase. It also exhibited a high degree of free radical scavenging potential. N-(1-adamantyl)-2-oxo-chromene-3-carboxamide (8), N-adamantan-1-yl-5-dimethyl-amino-1-naphthalenesulfonic acid (11) and N-(1-cyano-2H-isoindol-2-yl) adamantan-1-amine (12) were found to possess a high degree of multifunctionality with favourable physical-chemical properties for bioavailability and blood-brain barrier permeability. The ability of these heterocyclic adamantane amine derivatives as nitric oxide synthase inhibitors, calcium channel modulators, NMDAR inhibitors and effective antioxidants, indicate that they may find application as multifunctional drugs in neuroprotection.
authors.affiliation: Department of Pharmaceutical Chemistry, North-West University, Potchefstroom, South Africa.
authors.forename: Jacques
authors.initials: J
authors.lastname: Joubert
authors.forename: Sandra
authors.initials: S
authors.lastname: van Dyk
authors.forename: Ivan R
authors.initials: IR
authors.lastname: Green
authors.forename: Sarel F
authors.initials: SF
authors.lastname: Malan
mesh_terms: D000218:Adamantane / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D019001:Nitric Oxide Synthase; D000218:Adamantane