Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A

Eduard Dolusic, Pierre Larrieu, Céline Meinguet, Delphine Colette, Arnaud Rives, Sébastien Blanc, Thierry Ferain, Luc Pilotte, Vincent Stroobant, Johan Wouters, Benoît Van den Eynde, Bernard Masereel, Evelyne Delfourne, Raphaël Frédérick

Résultats de recherche: Recherche - Revue par des pairsArticle

Résumé

Tsitsikammamines are marine alkaloids whose structure is based on the pyrroloiminoquinone scaffold. These and related compounds have attracted attention due to various interesting biological properties, including cytotoxicity, topoisomerase inhibition, antimicrobial, antifungal and antimalarial activity. Indoleamine 2,3-dioxygenase (IDO1) is a well-established therapeutic target as an important factor in the tumor immune evasion mechanism. In this preliminary communication, we report the inhibitory activity of tsitsikammamine derivatives against IDO1. Tsitsikammamine A analogue 11b displays submicromolar potency in an enzymatic assay. A number of derivatives are also active in a cellular assay while showing little or no activity towards tryptophan 2,3-dioxygenase (TDO), a functionally related enzyme. This IDO1 inhibitory activity is rationalized by molecular modeling studies. An interest is thus established in this class of compounds as a potential source of lead compounds for the development of new pharmaceutically useful IDO1 inhibitors.

langueAnglais
Pages47-54
Nombre de pages8
journalBioorganic and medicinal chemistry letters
Volume23
Numéro1
Date de mise en ligne précoce24 nov. 2012
Les DOIs
étatPublié - 1 janv. 2013
EvénementJFB 2011. - Liege, Belgique
Durée: 19 mai 2011 → …

Empreinte digitale

Indoleamine-Pyrrole 2,3,-Dioxygenase
Alkaloids
Assays
Derivatives
tsitsikammamine A
Pyrroloiminoquinones
Tryptophan Oxygenase
Tumor Escape
Antimalarials
Enzyme Assays
Enzymes
Therapeutics
Lead compounds
Molecular modeling
Cytotoxicity
Scaffolds
Tumors
Display devices
Communication

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    Dolusic, Eduard ; Larrieu, Pierre ; Meinguet, Céline ; Colette, Delphine ; Rives, Arnaud ; Blanc, Sébastien ; Ferain, Thierry ; Pilotte, Luc ; Stroobant, Vincent ; Wouters, Johan ; Van den Eynde, Benoît ; Masereel, Bernard ; Delfourne, Evelyne ; Frédérick, Raphaël. / Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A. Dans: Bioorganic and medicinal chemistry letters. 2013 ; Vol 23, Numéro 1. p. 47-54
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    abstract = "Tsitsikammamines are marine alkaloids whose structure is based on the pyrroloiminoquinone scaffold. These and related compounds have attracted attention due to various interesting biological properties, including cytotoxicity, topoisomerase inhibition, antimicrobial, antifungal and antimalarial activity. Indoleamine 2,3-dioxygenase (IDO1) is a well-established therapeutic target as an important factor in the tumor immune evasion mechanism. In this preliminary communication, we report the inhibitory activity of tsitsikammamine derivatives against IDO1. Tsitsikammamine A analogue 11b displays submicromolar potency in an enzymatic assay. A number of derivatives are also active in a cellular assay while showing little or no activity towards tryptophan 2,3-dioxygenase (TDO), a functionally related enzyme. This IDO1 inhibitory activity is rationalized by molecular modeling studies. An interest is thus established in this class of compounds as a potential source of lead compounds for the development of new pharmaceutically useful IDO1 inhibitors.",
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    author = "Eduard Dolusic and Pierre Larrieu and Céline Meinguet and Delphine Colette and Arnaud Rives and Sébastien Blanc and Thierry Ferain and Luc Pilotte and Vincent Stroobant and Johan Wouters and {Van den Eynde}, Benoît and Bernard Masereel and Evelyne Delfourne and Raphaël Frédérick",
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    Dolusic, E, Larrieu, P, Meinguet, C, Colette, D, Rives, A, Blanc, S, Ferain, T, Pilotte, L, Stroobant, V, Wouters, J, Van den Eynde, B, Masereel, B, Delfourne, E & Frédérick, R 2013, 'Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A' Bioorganic and medicinal chemistry letters, VOL 23, Numéro 1, p. 47-54. DOI: 10.1016/j.bmcl.2012.11.036

    Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A. / Dolusic, Eduard; Larrieu, Pierre; Meinguet, Céline; Colette, Delphine; Rives, Arnaud; Blanc, Sébastien; Ferain, Thierry; Pilotte, Luc; Stroobant, Vincent; Wouters, Johan; Van den Eynde, Benoît; Masereel, Bernard; Delfourne, Evelyne; Frédérick, Raphaël.

    Dans: Bioorganic and medicinal chemistry letters, Vol 23, Numéro 1, 01.01.2013, p. 47-54.

    Résultats de recherche: Recherche - Revue par des pairsArticle

    TY - JOUR

    T1 - Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A

    AU - Dolusic,Eduard

    AU - Larrieu,Pierre

    AU - Meinguet,Céline

    AU - Colette,Delphine

    AU - Rives,Arnaud

    AU - Blanc,Sébastien

    AU - Ferain,Thierry

    AU - Pilotte,Luc

    AU - Stroobant,Vincent

    AU - Wouters,Johan

    AU - Van den Eynde,Benoît

    AU - Masereel,Bernard

    AU - Delfourne,Evelyne

    AU - Frédérick,Raphaël

    PY - 2013/1/1

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    N2 - Tsitsikammamines are marine alkaloids whose structure is based on the pyrroloiminoquinone scaffold. These and related compounds have attracted attention due to various interesting biological properties, including cytotoxicity, topoisomerase inhibition, antimicrobial, antifungal and antimalarial activity. Indoleamine 2,3-dioxygenase (IDO1) is a well-established therapeutic target as an important factor in the tumor immune evasion mechanism. In this preliminary communication, we report the inhibitory activity of tsitsikammamine derivatives against IDO1. Tsitsikammamine A analogue 11b displays submicromolar potency in an enzymatic assay. A number of derivatives are also active in a cellular assay while showing little or no activity towards tryptophan 2,3-dioxygenase (TDO), a functionally related enzyme. This IDO1 inhibitory activity is rationalized by molecular modeling studies. An interest is thus established in this class of compounds as a potential source of lead compounds for the development of new pharmaceutically useful IDO1 inhibitors.

    AB - Tsitsikammamines are marine alkaloids whose structure is based on the pyrroloiminoquinone scaffold. These and related compounds have attracted attention due to various interesting biological properties, including cytotoxicity, topoisomerase inhibition, antimicrobial, antifungal and antimalarial activity. Indoleamine 2,3-dioxygenase (IDO1) is a well-established therapeutic target as an important factor in the tumor immune evasion mechanism. In this preliminary communication, we report the inhibitory activity of tsitsikammamine derivatives against IDO1. Tsitsikammamine A analogue 11b displays submicromolar potency in an enzymatic assay. A number of derivatives are also active in a cellular assay while showing little or no activity towards tryptophan 2,3-dioxygenase (TDO), a functionally related enzyme. This IDO1 inhibitory activity is rationalized by molecular modeling studies. An interest is thus established in this class of compounds as a potential source of lead compounds for the development of new pharmaceutically useful IDO1 inhibitors.

    KW - Cancer immunology

    KW - Indoleamine 2,3-dioxygenase

    KW - Molecular modeling

    KW - Pyrroloiminoquinones

    KW - Tsitsikammamines

    U2 - 10.1016/j.bmcl.2012.11.036

    DO - 10.1016/j.bmcl.2012.11.036

    M3 - Article

    VL - 23

    SP - 47

    EP - 54

    JO - Bioorganic & medicinal chemistry letters

    T2 - Bioorganic & medicinal chemistry letters

    JF - Bioorganic & medicinal chemistry letters

    SN - 0960-894X

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