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

doi: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

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 journal › Article › peer-review

7 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 language	English
Pages (from-to)	5876-5885
Number of pages	10
Journal	Bioorganic & Medicinal Chemistry
Volume	21
Issue number	18
DOIs	https://doi.org/10.1016/j.bmc.2013.07.004
Publication status	Published - 15 Sept 2013

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Hampton, S. E., Schipani, A., Bosch-Navarrete, C., Recio, E., Kaiser, M., Kahnberg, P., González-Pacanowska, D., Johansson, N. G., & Gilbert, I. H. (2013). Investigation of acyclic uridine amide and 5'-amido nucleoside analogues as potential inhibitors of the Plasmodium falciparum dUTPase. Bioorganic & Medicinal Chemistry, 21(18), 5876-5885. https://doi.org/10.1016/j.bmc.2013.07.004

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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",

month = sep,

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doi = "10.1016/j.bmc.2013.07.004",

language = "English",

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journal = "Bioorganic \& Medicinal Chemistry",

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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

TY - JOUR

T1 - Investigation of acyclic uridine amide and 5'-amido nucleoside analogues as potential inhibitors of the Plasmodium falciparum dUTPase

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

N2 - 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.

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.

U2 - 10.1016/j.bmc.2013.07.004

DO - 10.1016/j.bmc.2013.07.004

M3 - Article

C2 - 23916149

SN - 0968-0896

VL - 21

SP - 5876

EP - 5885

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

IS - 18

ER -

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

Abstract

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