Novel functionalized melamine-based nitroheterocycles: synthesis and activity against trypanosomatid parasites

Alessandro Baliani, Valerie Peal, Ludovic Gros, Reto Brun, Marcel Kaiser, Michael P. Barrett, Ian H. Gilbert

    Research output: Contribution to journalArticle

    17 Citations (Scopus)

    Abstract

    Human African trypanosomiasis (HAT), caused by the protozoan parasite Trypanosoma brucei spp., is a major health problem in sub-Saharan Africa. New drugs are urgently required for the disease. Selective uptake of toxic compounds into trypanosomes has been achieved by exploiting plasma membrane transporters. For example, the P2 aminopurine transporter, along with other transporters, selectively concentrates melamine and benzamidine moieties into trypanosomes. We have previously reported the use of the melamine motif to selectively target nitrofuran to the trypanosome. In this paper we report the further investigation of the structure activity relationships and the effect of the introduction of different functionalized substituents onto the melamine unit. Most of the compounds tested in vitro for their trypanocidal activity showed activities in the submicromolar range against T. b. rhodesiense.

    Original languageEnglish
    Pages (from-to)1154-1166
    Number of pages13
    JournalOrganic and Biomolecular Chemistry
    Volume7
    Issue number6
    DOIs
    Publication statusPublished - 2009

    Keywords

    • BRUCEI-BRUCEI
    • NUCLEOSIDE TRANSPORTER
    • AFRICAN TRYPANOSOMES
    • CROSS-RESISTANCE
    • DIAMIDINE DRUGS
    • PENTAMIDINE
    • ADENOSINE
    • AFFINITY
    • ADDUCTS
    • CLONING

    Cite this

    Baliani, Alessandro ; Peal, Valerie ; Gros, Ludovic ; Brun, Reto ; Kaiser, Marcel ; Barrett, Michael P. ; Gilbert, Ian H. / Novel functionalized melamine-based nitroheterocycles: synthesis and activity against trypanosomatid parasites. In: Organic and Biomolecular Chemistry. 2009 ; Vol. 7, No. 6. pp. 1154-1166.
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    abstract = "Human African trypanosomiasis (HAT), caused by the protozoan parasite Trypanosoma brucei spp., is a major health problem in sub-Saharan Africa. New drugs are urgently required for the disease. Selective uptake of toxic compounds into trypanosomes has been achieved by exploiting plasma membrane transporters. For example, the P2 aminopurine transporter, along with other transporters, selectively concentrates melamine and benzamidine moieties into trypanosomes. We have previously reported the use of the melamine motif to selectively target nitrofuran to the trypanosome. In this paper we report the further investigation of the structure activity relationships and the effect of the introduction of different functionalized substituents onto the melamine unit. Most of the compounds tested in vitro for their trypanocidal activity showed activities in the submicromolar range against T. b. rhodesiense.",
    keywords = "BRUCEI-BRUCEI, NUCLEOSIDE TRANSPORTER, AFRICAN TRYPANOSOMES, CROSS-RESISTANCE, DIAMIDINE DRUGS, PENTAMIDINE, ADENOSINE, AFFINITY, ADDUCTS, CLONING",
    author = "Alessandro Baliani and Valerie Peal and Ludovic Gros and Reto Brun and Marcel Kaiser and Barrett, {Michael P.} and Gilbert, {Ian H.}",
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    Novel functionalized melamine-based nitroheterocycles: synthesis and activity against trypanosomatid parasites. / Baliani, Alessandro; Peal, Valerie; Gros, Ludovic; Brun, Reto; Kaiser, Marcel; Barrett, Michael P.; Gilbert, Ian H.

    In: Organic and Biomolecular Chemistry, Vol. 7, No. 6, 2009, p. 1154-1166.

    Research output: Contribution to journalArticle

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    T1 - Novel functionalized melamine-based nitroheterocycles: synthesis and activity against trypanosomatid parasites

    AU - Baliani, Alessandro

    AU - Peal, Valerie

    AU - Gros, Ludovic

    AU - Brun, Reto

    AU - Kaiser, Marcel

    AU - Barrett, Michael P.

    AU - Gilbert, Ian H.

    PY - 2009

    Y1 - 2009

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    AB - Human African trypanosomiasis (HAT), caused by the protozoan parasite Trypanosoma brucei spp., is a major health problem in sub-Saharan Africa. New drugs are urgently required for the disease. Selective uptake of toxic compounds into trypanosomes has been achieved by exploiting plasma membrane transporters. For example, the P2 aminopurine transporter, along with other transporters, selectively concentrates melamine and benzamidine moieties into trypanosomes. We have previously reported the use of the melamine motif to selectively target nitrofuran to the trypanosome. In this paper we report the further investigation of the structure activity relationships and the effect of the introduction of different functionalized substituents onto the melamine unit. Most of the compounds tested in vitro for their trypanocidal activity showed activities in the submicromolar range against T. b. rhodesiense.

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    KW - NUCLEOSIDE TRANSPORTER

    KW - AFRICAN TRYPANOSOMES

    KW - CROSS-RESISTANCE

    KW - DIAMIDINE DRUGS

    KW - PENTAMIDINE

    KW - ADENOSINE

    KW - AFFINITY

    KW - ADDUCTS

    KW - CLONING

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