title: 4-Substituted 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as a Novel Class of HIV-1 Integrase Inhibitors.
abstract: A series of 2-hydroxy-1,3-dioxoisoquinoline-4-carboxamides featuring an N-hydroxyimide chelating functionality was evaluated for their inhibitory properties against human immunodeficiency virus type 1 integrase (HIV-1 IN). Several derivatives displayed low nanomolar IC50 values comparable to that of the clinically used raltegravir. A marked effect of one compound on both primary IN-catalyzed reactions, strand transfer (ST), and 3' processing (3'-P), emphasizes a novel IN inhibition mechanism establishing it as a potential new generation IN inhibitor. Substitution of the 2-hydroxyisoquinoline-1,3-dione scaffold at position 4 by carboxamido chains was beneficial for antiviral activity since reproducible low micromolar anti-HIV activities were obtained for the first time within this scaffold.
authors.affiliation: Université Lille Nord de France , F-59000 Lille, France ; Université Lille 1 Sciences & Technologies , EA 4478 Chimie Moléculaire et Formulation, F-59655 Villeneuve d'Ascq, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Billamboz
authors.affiliation: Université Lille Nord de France , F-59000 Lille, France ; Université Lille 1 Sciences & Technologies , EA 4478 Chimie Moléculaire et Formulation, F-59655 Villeneuve d'Ascq, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Suchaud
authors.affiliation: Université Lille Nord de France , F-59000 Lille, France ; Université Lille 1 Sciences & Technologies , EA 4478 Chimie Moléculaire et Formulation, F-59655 Villeneuve d'Ascq, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bailly
authors.affiliation: Université Lille Nord de France , F-59000 Lille, France ; Université Lille 1 Sciences & Technologies , EA 4478 Chimie Moléculaire et Formulation, F-59655 Villeneuve d'Ascq, France.
authors.forename: Cedric
authors.initials: C
authors.lastname: Lion
authors.affiliation: KU Leuven , Molecular Virology and Gene Therapy (VCTB+5), Kapucijnenvoer 33, B-3000 Leuven, Flanders, Belgium.
authors.forename: Jonas
authors.initials: J
authors.lastname: Demeulemeester
authors.affiliation: UMR 5234 CNRS, Université Bordeaux Segalen , 146 Rue Léo Saignat, F-33076 Bordeaux, France.
authors.forename: Christina
authors.initials: C
authors.lastname: Calmels
authors.affiliation: UMR 5234 CNRS, Université Bordeaux Segalen , 146 Rue Léo Saignat, F-33076 Bordeaux, France.
authors.forename: Marie-Line
authors.initials: ML
authors.lastname: Andréola
authors.affiliation: KU Leuven , Molecular Virology and Gene Therapy (VCTB+5), Kapucijnenvoer 33, B-3000 Leuven, Flanders, Belgium.
authors.forename: Frauke
authors.initials: F
authors.lastname: Christ
authors.affiliation: KU Leuven , Molecular Virology and Gene Therapy (VCTB+5), Kapucijnenvoer 33, B-3000 Leuven, Flanders, Belgium.
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.affiliation: Université Lille Nord de France , F-59000 Lille, France ; Université Lille 1 Sciences & Technologies , EA 4478 Chimie Moléculaire et Formulation, F-59655 Villeneuve d'Ascq, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Cotelle
keywords: 2-hydroxy-1,3-dioxoisoquinoline-4-carboxamide; 3′ processing; HIV; antiretroviral; integrase