Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid as HIV-1 integrase inhibitor

Pierre Vandurm, Christine Cauvin, Allan Guiguen, Benoît Georges, Kiet Le Van, Valérie Martinelli, Christelle Cardona, Gladys Mbemba, Jean François Mouscadet, László Hevesi, Carine Van Lint, Johan Wouters

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

Ethyl [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl]-4-hydroxy-2-oxo-3-butenoate 1 and [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid 2 were synthesized as potential HIV-1 integrase inhibitors and evaluated for their enzymatic and antiviral activity, acidic compound 2 being more potent than ester compound 1. X-ray diffraction analyses and theoretical calculations show that the diketoacid chain of compound 2 is preferentially coplanar with the quinolinone ring (dihedral angle of 0-30°). Docking studies suggest binding modes in agreement with structure-activity relationships.

langue originaleAnglais
Pages (de - à)4806-4809
Nombre de pages4
journalBioorganic & Medicinal Chemistry Letters
Volume19
Numéro de publication16
Les DOIs
étatPublié - 15 août 2009

Empreinte digitale

HIV Integrase Inhibitors
Integrase Inhibitors
Quinolones
Dihedral angle
Structure-Activity Relationship
X-Ray Diffraction
Antiviral Agents
Esters
Theoretical Models
X ray diffraction
Acids
p31 integrase protein, Human immunodeficiency virus 1

mots-clés

    Citer ceci

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    title = "Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-buteno{\"i}c acid as HIV-1 integrase inhibitor",
    abstract = "Ethyl [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl]-4-hydroxy-2-oxo-3-butenoate 1 and [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-buteno{\"i}c acid 2 were synthesized as potential HIV-1 integrase inhibitors and evaluated for their enzymatic and antiviral activity, acidic compound 2 being more potent than ester compound 1. X-ray diffraction analyses and theoretical calculations show that the diketoacid chain of compound 2 is preferentially coplanar with the quinolinone ring (dihedral angle of 0-30°). Docking studies suggest binding modes in agreement with structure-activity relationships.",
    keywords = "β-Diketo, HIV-1, Integrase inhibitors, Quinolinone",
    author = "Pierre Vandurm and Christine Cauvin and Allan Guiguen and Beno{\^i}t Georges and Van, {Kiet Le} and Val{\'e}rie Martinelli and Christelle Cardona and Gladys Mbemba and Mouscadet, {Jean Fran{\cc}ois} and L{\'a}szl{\'o} Hevesi and Lint, {Carine Van} and Johan Wouters",
    year = "2009",
    month = "8",
    day = "15",
    doi = "10.1016/j.bmcl.2009.06.044",
    language = "English",
    volume = "19",
    pages = "4806--4809",
    journal = "Bioorganic and medicinal chemistry letters",
    issn = "0960-894X",
    publisher = "Elsevier Limited",
    number = "16",

    }

    Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid as HIV-1 integrase inhibitor. / Vandurm, Pierre; Cauvin, Christine; Guiguen, Allan; Georges, Benoît; Van, Kiet Le; Martinelli, Valérie; Cardona, Christelle; Mbemba, Gladys; Mouscadet, Jean François; Hevesi, László; Lint, Carine Van; Wouters, Johan.

    Dans: Bioorganic & Medicinal Chemistry Letters, Vol 19, Numéro 16, 15.08.2009, p. 4806-4809.

    Résultats de recherche: Contribution à un journal/une revueArticle

    TY - JOUR

    T1 - Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid as HIV-1 integrase inhibitor

    AU - Vandurm, Pierre

    AU - Cauvin, Christine

    AU - Guiguen, Allan

    AU - Georges, Benoît

    AU - Van, Kiet Le

    AU - Martinelli, Valérie

    AU - Cardona, Christelle

    AU - Mbemba, Gladys

    AU - Mouscadet, Jean François

    AU - Hevesi, László

    AU - Lint, Carine Van

    AU - Wouters, Johan

    PY - 2009/8/15

    Y1 - 2009/8/15

    N2 - Ethyl [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl]-4-hydroxy-2-oxo-3-butenoate 1 and [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid 2 were synthesized as potential HIV-1 integrase inhibitors and evaluated for their enzymatic and antiviral activity, acidic compound 2 being more potent than ester compound 1. X-ray diffraction analyses and theoretical calculations show that the diketoacid chain of compound 2 is preferentially coplanar with the quinolinone ring (dihedral angle of 0-30°). Docking studies suggest binding modes in agreement with structure-activity relationships.

    AB - Ethyl [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl]-4-hydroxy-2-oxo-3-butenoate 1 and [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid 2 were synthesized as potential HIV-1 integrase inhibitors and evaluated for their enzymatic and antiviral activity, acidic compound 2 being more potent than ester compound 1. X-ray diffraction analyses and theoretical calculations show that the diketoacid chain of compound 2 is preferentially coplanar with the quinolinone ring (dihedral angle of 0-30°). Docking studies suggest binding modes in agreement with structure-activity relationships.

    KW - β-Diketo

    KW - HIV-1

    KW - Integrase inhibitors

    KW - Quinolinone

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    U2 - 10.1016/j.bmcl.2009.06.044

    DO - 10.1016/j.bmcl.2009.06.044

    M3 - Article

    VL - 19

    SP - 4806

    EP - 4809

    JO - Bioorganic and medicinal chemistry letters

    JF - Bioorganic and medicinal chemistry letters

    SN - 0960-894X

    IS - 16

    ER -