title: Novel inhibitors of neuronal nitric oxide synthase with potent antioxidant properties.
abstract: A series of hybrid compounds possessing an nNOS pharmacophore linked to an antioxidant fragment has been synthesized. Among them, compound 8d, a propofol derivative, displayed the greatest dual potencies against nNOS (IC(50)=0.12 microM) and lipid peroxidation (IC(50)=0.4 microM) accompanied with e/nNOS selectivity (67.5). This shows that nNOS was able to accommodate very bulky groups such as di-tert-butyl or di-iso-propyl phenol in its active site.
authors.affiliation: Department of Medicinal Chemistry, Beaufour-Ipsen Research Laboratories, Institut Henri Beaufour, 5, Avenue du Canada, 91966 Les Ulis Cedex, France. serge.auvin@beaufour-ipsen.com
authors.forename: Serge
authors.initials: S
authors.lastname: Auvin
authors.forename: Michel
authors.initials: M
authors.lastname: Auguet
authors.forename: Edith
authors.initials: E
authors.lastname: Navet
authors.forename: Jeremiah J
authors.initials: JJ
authors.lastname: Harnett
authors.forename: Isabelle
authors.initials: I
authors.lastname: Viossat
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Schulz
authors.forename: Dennis
authors.initials: D
authors.lastname: Bigg
authors.forename: Pierre E
authors.initials: PE
authors.lastname: Chabrier
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D015742:Propofol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D013379:Substrate Specificity
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D015742:Propofol