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Design, Synthesis, and Evaluation of 5 '-Diphenyl Nucleoside Analogues as Inhibitors of the Plasmodium falciparum dUTPase

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Design, Synthesis, and Evaluation of 5 '-Diphenyl Nucleoside Analogues as Inhibitors of the Plasmodium falciparum dUTPase. / Hampton, Shahienaz E.; Baragana, Beatriz; Schipani, Alessandro; Bosch-Navarrete, Cristina; Alexander Musso-Buendia, J.; Recio, Eliseo; Kaiser, Marcel; Whittingham, Jean L.; Roberts, Shirley M.; Shevtsov, Mikhail; Brannigan, James A.; Kahnberg, Pia; Brun, Reto; Wilson, Keith S.; Gonzalez-Pacanowska, Dolores; Johansson, Nils Gunnar; Gilbert, Ian H.

In: ChemMedChem, Vol. 6, No. 10, 04.10.2011, p. 1816-1831.

Research output: Contribution to journalArticle

Harvard

Hampton, SE, Baragana, B, Schipani, A, Bosch-Navarrete, C, Alexander Musso-Buendia, J, Recio, E, Kaiser, M, Whittingham, JL, Roberts, SM, Shevtsov, M, Brannigan, JA, Kahnberg, P, Brun, R, Wilson, KS, Gonzalez-Pacanowska, D, Johansson, NG & Gilbert, IH 2011, 'Design, Synthesis, and Evaluation of 5 '-Diphenyl Nucleoside Analogues as Inhibitors of the Plasmodium falciparum dUTPase' ChemMedChem, vol 6, no. 10, pp. 1816-1831.

APA

Hampton, S. E., Baragana, B., Schipani, A., Bosch-Navarrete, C., Alexander Musso-Buendia, J., Recio, E., Kaiser, M., Whittingham, J. L., Roberts, S. M., Shevtsov, M., Brannigan, J. A., Kahnberg, P., Brun, R., Wilson, K. S., Gonzalez-Pacanowska, D., Johansson, N. G., & Gilbert, I. H. (2011). Design, Synthesis, and Evaluation of 5 '-Diphenyl Nucleoside Analogues as Inhibitors of the Plasmodium falciparum dUTPase. ChemMedChem, 6(10), 1816-1831doi: 10.1002/cmdc.201100255

Vancouver

Hampton SE, Baragana B, Schipani A, Bosch-Navarrete C, Alexander Musso-Buendia J, Recio E et al. Design, Synthesis, and Evaluation of 5 '-Diphenyl Nucleoside Analogues as Inhibitors of the Plasmodium falciparum dUTPase. ChemMedChem. 2011 Oct 4;6(10):1816-1831.

Author

Hampton, Shahienaz E.; Baragana, Beatriz; Schipani, Alessandro; Bosch-Navarrete, Cristina; Alexander Musso-Buendia, J.; Recio, Eliseo; Kaiser, Marcel; Whittingham, Jean L.; Roberts, Shirley M.; Shevtsov, Mikhail; Brannigan, James A.; Kahnberg, Pia; Brun, Reto; Wilson, Keith S.; Gonzalez-Pacanowska, Dolores; Johansson, Nils Gunnar; Gilbert, Ian H. / Design, Synthesis, and Evaluation of 5 '-Diphenyl Nucleoside Analogues as Inhibitors of the Plasmodium falciparum dUTPase.

In: ChemMedChem, Vol. 6, No. 10, 04.10.2011, p. 1816-1831.

Research output: Contribution to journalArticle

Bibtex - Download

@article{10796694989c4b2ba0af15376007268e,
title = "Design, Synthesis, and Evaluation of 5 '-Diphenyl Nucleoside Analogues as Inhibitors of the Plasmodium falciparum dUTPase",
author = "Hampton, {Shahienaz E.} and Beatriz Baragana and Alessandro Schipani and Cristina Bosch-Navarrete and {Alexander Musso-Buendia}, J. and Eliseo Recio and Marcel Kaiser and Whittingham, {Jean L.} and Roberts, {Shirley M.} and Mikhail Shevtsov and Brannigan, {James A.} and Pia Kahnberg and Reto Brun and Wilson, {Keith S.} and Dolores Gonzalez-Pacanowska and Johansson, {Nils Gunnar} and Gilbert, {Ian H.}",
year = "2011",
volume = "6",
number = "10",
pages = "1816--1831",
journal = "ChemMedChem",
issn = "1860-7179",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Design, Synthesis, and Evaluation of 5 '-Diphenyl Nucleoside Analogues as Inhibitors of the Plasmodium falciparum dUTPase

A1 - Hampton,Shahienaz E.

A1 - Baragana,Beatriz

A1 - Schipani,Alessandro

A1 - Bosch-Navarrete,Cristina

A1 - Alexander Musso-Buendia,J.

A1 - Recio,Eliseo

A1 - Kaiser,Marcel

A1 - Whittingham,Jean L.

A1 - Roberts,Shirley M.

A1 - Shevtsov,Mikhail

A1 - Brannigan,James A.

A1 - Kahnberg,Pia

A1 - Brun,Reto

A1 - Wilson,Keith S.

A1 - Gonzalez-Pacanowska,Dolores

A1 - Johansson,Nils Gunnar

A1 - Gilbert,Ian H.

AU - Hampton,Shahienaz E.

AU - Baragana,Beatriz

AU - Schipani,Alessandro

AU - Bosch-Navarrete,Cristina

AU - Alexander Musso-Buendia,J.

AU - Recio,Eliseo

AU - Kaiser,Marcel

AU - Whittingham,Jean L.

AU - Roberts,Shirley M.

AU - Shevtsov,Mikhail

AU - Brannigan,James A.

AU - Kahnberg,Pia

AU - Brun,Reto

AU - Wilson,Keith S.

AU - Gonzalez-Pacanowska,Dolores

AU - Johansson,Nils Gunnar

AU - Gilbert,Ian H.

PY - 2011/10/4

Y1 - 2011/10/4

N2 - <p>Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) is a potential drug target for malaria. We previously reported some 5'-tritylated deoxyuridine analogues (both cyclic and acyclic) as selective inhibitors of the Plasmodium falciparum dUTPase. Modelling studies indicated that it might be possible to replace the trityl group with a diphenyl moiety, as two of the phenyl groups are buried, whereas the third is exposed to solvent. Herein we report the synthesis and evaluation of some diphenyl analogues that have lower lipophilicity and molecular weight than the trityl lead compound. Co-crystal structures show that the diphenyl inhibitors bind in a similar manner to the corresponding trityl derivatives, with the two phenyl moieties occupying the predicted buried phenyl binding sites. The diphenyl compounds prepared show similar or slightly lower inhibition of PfdUTPase, and similar or weaker inhibition of parasite growth than the trityl compounds.</p>

AB - <p>Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) is a potential drug target for malaria. We previously reported some 5'-tritylated deoxyuridine analogues (both cyclic and acyclic) as selective inhibitors of the Plasmodium falciparum dUTPase. Modelling studies indicated that it might be possible to replace the trityl group with a diphenyl moiety, as two of the phenyl groups are buried, whereas the third is exposed to solvent. Herein we report the synthesis and evaluation of some diphenyl analogues that have lower lipophilicity and molecular weight than the trityl lead compound. Co-crystal structures show that the diphenyl inhibitors bind in a similar manner to the corresponding trityl derivatives, with the two phenyl moieties occupying the predicted buried phenyl binding sites. The diphenyl compounds prepared show similar or slightly lower inhibition of PfdUTPase, and similar or weaker inhibition of parasite growth than the trityl compounds.</p>

KW - antiprotozoal agents

KW - drug design

KW - dUTPase

KW - malaria

KW - nucleosides

KW - DRUG

KW - TARGET

U2 - 10.1002/cmdc.201100255

DO - 10.1002/cmdc.201100255

M1 - Article

JO - ChemMedChem

JF - ChemMedChem

SN - 1860-7179

IS - 10

VL - 6

SP - 1816

EP - 1831

ER -

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