Résumé

With the aim to explore the interest of the thiosemicarbazide scaffold for the inhibition of the indoleamine 2,3-dioxygenase (IDO), a promising therapeutic target for anticancer immunotherapy, a series of 32 phenylthiosemicarbazide derivatives was prepared and their IDO inhibition evaluated. Our study demonstrated that among these derivatives, compound 14 characterized with a 4-cyanophenyl group on the thiosemicarbazide was the more potent IDO inhibitor in this series being endowed with an IC50 of 1.2 μM. The SAR depicted showed that substitution in the 3- and 4-position relative to the phenylthiosemicarbazide are very promising whereas substitution in the 2-position always leads to less potent or inactive derivatives. In fact the study highlighted a novel interesting scaffold for IDO inhibition for further development.

langueAnglais
Pages96-105
Nombre de pages10
journalEuropean Journal of Medicinal Chemistry
Volume82
Les DOIs
étatPublié - 23 juil. 2014

Empreinte digitale

Indoleamine-Pyrrole 2,3,-Dioxygenase
Derivatives
Scaffolds
Substitution reactions
Immunotherapy
thiosemicarbazide

mots-clés

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    @article{b9a56fcfb72e48e79ce34f21e4871b7d,
    title = "Thiosemicarbazide, a fragment with promising indolamine-2,3-dioxygenase (IDO) inhibition properties",
    abstract = "With the aim to explore the interest of the thiosemicarbazide scaffold for the inhibition of the indoleamine 2,3-dioxygenase (IDO), a promising therapeutic target for anticancer immunotherapy, a series of 32 phenylthiosemicarbazide derivatives was prepared and their IDO inhibition evaluated. Our study demonstrated that among these derivatives, compound 14 characterized with a 4-cyanophenyl group on the thiosemicarbazide was the more potent IDO inhibitor in this series being endowed with an IC50 of 1.2 μM. The SAR depicted showed that substitution in the 3- and 4-position relative to the phenylthiosemicarbazide are very promising whereas substitution in the 2-position always leads to less potent or inactive derivatives. In fact the study highlighted a novel interesting scaffold for IDO inhibition for further development.",
    keywords = "IDO, Immunotherapy, Indoleamine 2,3-dioxygenase, Molecular modelling, Thiosemicarbazide",
    author = "Silvia Serra and Laurence Moineaux and Christelle Vancraeynest and Bernard Masereel and Johan Wouters and Lionel Pochet and Rapha{\"e}l Fr{\'e}d{\'e}rick",
    year = "2014",
    month = "7",
    day = "23",
    doi = "10.1016/j.ejmech.2014.05.044",
    language = "English",
    volume = "82",
    pages = "96--105",
    journal = "European Journal of Medicinal Chemistry",
    issn = "0223-5234",
    publisher = "Elsevier Masson SAS",

    }

    TY - JOUR

    T1 - Thiosemicarbazide, a fragment with promising indolamine-2,3-dioxygenase (IDO) inhibition properties

    AU - Serra,Silvia

    AU - Moineaux,Laurence

    AU - Vancraeynest,Christelle

    AU - Masereel,Bernard

    AU - Wouters,Johan

    AU - Pochet,Lionel

    AU - Frédérick,Raphaël

    PY - 2014/7/23

    Y1 - 2014/7/23

    N2 - With the aim to explore the interest of the thiosemicarbazide scaffold for the inhibition of the indoleamine 2,3-dioxygenase (IDO), a promising therapeutic target for anticancer immunotherapy, a series of 32 phenylthiosemicarbazide derivatives was prepared and their IDO inhibition evaluated. Our study demonstrated that among these derivatives, compound 14 characterized with a 4-cyanophenyl group on the thiosemicarbazide was the more potent IDO inhibitor in this series being endowed with an IC50 of 1.2 μM. The SAR depicted showed that substitution in the 3- and 4-position relative to the phenylthiosemicarbazide are very promising whereas substitution in the 2-position always leads to less potent or inactive derivatives. In fact the study highlighted a novel interesting scaffold for IDO inhibition for further development.

    AB - With the aim to explore the interest of the thiosemicarbazide scaffold for the inhibition of the indoleamine 2,3-dioxygenase (IDO), a promising therapeutic target for anticancer immunotherapy, a series of 32 phenylthiosemicarbazide derivatives was prepared and their IDO inhibition evaluated. Our study demonstrated that among these derivatives, compound 14 characterized with a 4-cyanophenyl group on the thiosemicarbazide was the more potent IDO inhibitor in this series being endowed with an IC50 of 1.2 μM. The SAR depicted showed that substitution in the 3- and 4-position relative to the phenylthiosemicarbazide are very promising whereas substitution in the 2-position always leads to less potent or inactive derivatives. In fact the study highlighted a novel interesting scaffold for IDO inhibition for further development.

    KW - IDO

    KW - Immunotherapy

    KW - Indoleamine 2,3-dioxygenase

    KW - Molecular modelling

    KW - Thiosemicarbazide

    UR - http://www.scopus.com/inward/record.url?scp=84901684225&partnerID=8YFLogxK

    U2 - 10.1016/j.ejmech.2014.05.044

    DO - 10.1016/j.ejmech.2014.05.044

    M3 - Article

    VL - 82

    SP - 96

    EP - 105

    JO - European Journal of Medicinal Chemistry

    T2 - European Journal of Medicinal Chemistry

    JF - European Journal of Medicinal Chemistry

    SN - 0223-5234

    ER -