Investigation of acyclic uridine amide and 5'-amido nucleoside analogues as potential inhibitors of the Plasmodium falciparum dUTPase

Shahienaz E. Hampton, Alessandro Schipani, Cristina Bosch-Navarrete, Eliseo Recio, Marcel Kaiser, Pia Kahnberg, Dolores González-Pacanowska, Nils Gunnar Johansson, Ian H. Gilbert

    Research output: Contribution to journalArticle

    3 Citations (Scopus)

    Abstract

    Previously we have shown that trityl and diphenyl deoxyuridine derivatives and their acyclic analogues can inhibit Plasmodium falciparum dUTPase (PfdUTPase). We report the synthesis of conformationally restrained amide derivatives as inhibitors PfdUTPase, including both acyclic and cyclic examples. Activity was dependent on the orientation and location of the amide constraining group. In the case of the acyclic series, we were able to obtain amide-constrained analogues which showed similar or greater potency than the unconstrained analogues. Unfortunately these compounds showed lower selectivity in cellular assays.
    Original languageEnglish
    Pages (from-to)5876-5885
    Number of pages10
    JournalBioorganic & Medicinal Chemistry
    Volume21
    Issue number18
    DOIs
    Publication statusPublished - 15 Sep 2013

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    Uridine
    Plasmodium falciparum
    Nucleosides
    Amides
    Derivatives
    Deoxyuridine
    Assays
    dUTP pyrophosphatase

    Cite this

    Hampton, Shahienaz E. ; Schipani, Alessandro ; Bosch-Navarrete, Cristina ; Recio, Eliseo ; Kaiser, Marcel ; Kahnberg, Pia ; González-Pacanowska, Dolores ; Johansson, Nils Gunnar ; Gilbert, Ian H. / Investigation of acyclic uridine amide and 5'-amido nucleoside analogues as potential inhibitors of the Plasmodium falciparum dUTPase. In: Bioorganic & Medicinal Chemistry. 2013 ; Vol. 21, No. 18. pp. 5876-5885.
    @article{6d8387cd76d244e9a25f0558d42d33fb,
    title = "Investigation of acyclic uridine amide and 5'-amido nucleoside analogues as potential inhibitors of the Plasmodium falciparum dUTPase",
    abstract = "Previously we have shown that trityl and diphenyl deoxyuridine derivatives and their acyclic analogues can inhibit Plasmodium falciparum dUTPase (PfdUTPase). We report the synthesis of conformationally restrained amide derivatives as inhibitors PfdUTPase, including both acyclic and cyclic examples. Activity was dependent on the orientation and location of the amide constraining group. In the case of the acyclic series, we were able to obtain amide-constrained analogues which showed similar or greater potency than the unconstrained analogues. Unfortunately these compounds showed lower selectivity in cellular assays.",
    author = "Hampton, {Shahienaz E.} and Alessandro Schipani and Cristina Bosch-Navarrete and Eliseo Recio and Marcel Kaiser and Pia Kahnberg and Dolores Gonz{\'a}lez-Pacanowska and Johansson, {Nils Gunnar} and Gilbert, {Ian H.}",
    year = "2013",
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    doi = "10.1016/j.bmc.2013.07.004",
    language = "English",
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    pages = "5876--5885",
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    Hampton, SE, Schipani, A, Bosch-Navarrete, C, Recio, E, Kaiser, M, Kahnberg, P, González-Pacanowska, D, Johansson, NG & Gilbert, IH 2013, 'Investigation of acyclic uridine amide and 5'-amido nucleoside analogues as potential inhibitors of the Plasmodium falciparum dUTPase', Bioorganic & Medicinal Chemistry, vol. 21, no. 18, pp. 5876-5885. https://doi.org/10.1016/j.bmc.2013.07.004

    Investigation of acyclic uridine amide and 5'-amido nucleoside analogues as potential inhibitors of the Plasmodium falciparum dUTPase. / Hampton, Shahienaz E.; Schipani, Alessandro; Bosch-Navarrete, Cristina; Recio, Eliseo; Kaiser, Marcel; Kahnberg, Pia; González-Pacanowska, Dolores; Johansson, Nils Gunnar; Gilbert, Ian H.

    In: Bioorganic & Medicinal Chemistry, Vol. 21, No. 18, 15.09.2013, p. 5876-5885.

    Research output: Contribution to journalArticle

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    AU - Hampton, Shahienaz E.

    AU - Schipani, Alessandro

    AU - Bosch-Navarrete, Cristina

    AU - Recio, Eliseo

    AU - Kaiser, Marcel

    AU - Kahnberg, Pia

    AU - González-Pacanowska, Dolores

    AU - Johansson, Nils Gunnar

    AU - Gilbert, Ian H.

    PY - 2013/9/15

    Y1 - 2013/9/15

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    AB - Previously we have shown that trityl and diphenyl deoxyuridine derivatives and their acyclic analogues can inhibit Plasmodium falciparum dUTPase (PfdUTPase). We report the synthesis of conformationally restrained amide derivatives as inhibitors PfdUTPase, including both acyclic and cyclic examples. Activity was dependent on the orientation and location of the amide constraining group. In the case of the acyclic series, we were able to obtain amide-constrained analogues which showed similar or greater potency than the unconstrained analogues. Unfortunately these compounds showed lower selectivity in cellular assays.

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