Selective delivery of 2-hydroxy APA to Trypanosoma brucei using the melamine motif

Nina Klee; Pui Ee Wong; Beatriz Baragana; Farah El Mazouni; Margaret A. Phillips; Michael P. Barrett; Ian H. Gilbert

doi:10.1016/j.bmcl.2010.06.070

Selective delivery of 2-hydroxy APA to Trypanosoma brucei using the melamine motif

Nina Klee, Pui Ee Wong, Beatriz Baragana, Farah El Mazouni, Margaret A. Phillips, Michael P. Barrett, Ian H. Gilbert

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12 Citations (Scopus)

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Abstract

Trypanosoma brucei, the parasite that causes human African trypanosomiasis, is auxotrophic for purines and has specialist nucleoside transporters to import these metabolites. In particular, the P2 aminopurine transporter can also selectively accumulate melamine derivatives. In this Letter, we report the coupling of the melamine moiety to 2-hydroxy APA, a potent ornithine decarboxylase inhibitor, with the aim of selectively delivering this compound to the parasite. The best compound described here shows an increased in vitro trypanocidal activity compared with the parent. (C) 2010 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	4364-4366
Number of pages	3
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	20
Issue number	15
DOIs	https://doi.org/10.1016/j.bmcl.2010.06.070
Publication status	Published - 1 Aug 2010

Keywords

Trypanosoma brucei
P2 transporter
Ornithine decarboxylase
UNUSUAL ADENOSINE TRANSPORTER
ORNITHINE-DECARBOXYLASE
CROSS-RESISTANCE
DIAMIDINE DRUGS
PENTAMIDINE
NITROHETEROCYCLES
POLYAMINES
FUTURE

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10.1016/j.bmcl.2010.06.070Licence: CC BY

http://ukpmc.ac.uk/articles/PMC2935964

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Embargo ends: 31/12/99

Aref#d: 19815. Wellcome Trust Centre for Drug Discovery (Strategic Award)
Fairlamb, A. (Investigator), Ferguson, M. (Investigator) & Frearson, J. (Investigator)
1/01/08 → 31/12/12
Project: Research

Cite this

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title = "Selective delivery of 2-hydroxy APA to Trypanosoma brucei using the melamine motif",

abstract = "Trypanosoma brucei, the parasite that causes human African trypanosomiasis, is auxotrophic for purines and has specialist nucleoside transporters to import these metabolites. In particular, the P2 aminopurine transporter can also selectively accumulate melamine derivatives. In this Letter, we report the coupling of the melamine moiety to 2-hydroxy APA, a potent ornithine decarboxylase inhibitor, with the aim of selectively delivering this compound to the parasite. The best compound described here shows an increased in vitro trypanocidal activity compared with the parent. (C) 2010 Elsevier Ltd. All rights reserved.",

keywords = "Trypanosoma brucei, P2 transporter, Ornithine decarboxylase, UNUSUAL ADENOSINE TRANSPORTER, ORNITHINE-DECARBOXYLASE, CROSS-RESISTANCE, DIAMIDINE DRUGS, PENTAMIDINE, NITROHETEROCYCLES, POLYAMINES, FUTURE",

author = "Nina Klee and Wong, {Pui Ee} and Beatriz Baragana and {El Mazouni}, Farah and Phillips, {Margaret A.} and Barrett, {Michael P.} and Gilbert, {Ian H.}",

year = "2010",

month = aug,

day = "1",

doi = "10.1016/j.bmcl.2010.06.070",

language = "English",

volume = "20",

pages = "4364--4366",

journal = "Bioorganic & Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier",

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TY - JOUR

T1 - Selective delivery of 2-hydroxy APA to Trypanosoma brucei using the melamine motif

AU - Klee, Nina

AU - Wong, Pui Ee

AU - Baragana, Beatriz

AU - El Mazouni, Farah

AU - Phillips, Margaret A.

AU - Barrett, Michael P.

AU - Gilbert, Ian H.

PY - 2010/8/1

Y1 - 2010/8/1

N2 - Trypanosoma brucei, the parasite that causes human African trypanosomiasis, is auxotrophic for purines and has specialist nucleoside transporters to import these metabolites. In particular, the P2 aminopurine transporter can also selectively accumulate melamine derivatives. In this Letter, we report the coupling of the melamine moiety to 2-hydroxy APA, a potent ornithine decarboxylase inhibitor, with the aim of selectively delivering this compound to the parasite. The best compound described here shows an increased in vitro trypanocidal activity compared with the parent. (C) 2010 Elsevier Ltd. All rights reserved.

AB - Trypanosoma brucei, the parasite that causes human African trypanosomiasis, is auxotrophic for purines and has specialist nucleoside transporters to import these metabolites. In particular, the P2 aminopurine transporter can also selectively accumulate melamine derivatives. In this Letter, we report the coupling of the melamine moiety to 2-hydroxy APA, a potent ornithine decarboxylase inhibitor, with the aim of selectively delivering this compound to the parasite. The best compound described here shows an increased in vitro trypanocidal activity compared with the parent. (C) 2010 Elsevier Ltd. All rights reserved.

KW - Trypanosoma brucei

KW - P2 transporter

KW - Ornithine decarboxylase

KW - UNUSUAL ADENOSINE TRANSPORTER

KW - ORNITHINE-DECARBOXYLASE

KW - CROSS-RESISTANCE

KW - DIAMIDINE DRUGS

KW - PENTAMIDINE

KW - NITROHETEROCYCLES

KW - POLYAMINES

KW - FUTURE

U2 - 10.1016/j.bmcl.2010.06.070

DO - 10.1016/j.bmcl.2010.06.070

M3 - Article

C2 - 20615694

SN - 0960-894X

VL - 20

SP - 4364

EP - 4366

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 15

ER -

Selective delivery of 2-hydroxy APA to Trypanosoma brucei using the melamine motif

Abstract

Keywords

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Aref#d: 19815. Wellcome Trust Centre for Drug Discovery (Strategic Award)

Cite this