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

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

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

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

Keywords

Ornithine decarboxylase
P2 transporter
Trypanosoma brucei

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmcl.2010.06.070

Cite this

@article{c1107ed6b11341f58391d1010427b997,

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.",

keywords = "Ornithine decarboxylase, P2 transporter, Trypanosoma brucei",

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

note = "Funding Information: We would like to acknowledge the following for funding: Studienstiftung des deutschen Volkes for a studentship (N.K.); the Wellcome Trust (WT 083481 ) (Dundee); the National Institutes of Health Grant ( R01 AI34432 ) (M.A.P.); and the Welch Foundation Grant I-1257 (M.A.P.). M.A.P. holds the Carolyn R. Bacon Professorship in Medical Science and Education. ",

year = "2010",

month = aug,

day = "1",

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

language = "English (US)",

volume = "20",

pages = "4364--4366",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "15",

}

TY - JOUR

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

AU - Klee, Nina

AU - Wong, Pui Ee

AU - Baragaña, Beatriz

AU - Mazouni, Farah El

AU - Phillips, Margaret A.

AU - Barrett, Michael P.

AU - Gilbert, Ian H.

N1 - Funding Information: We would like to acknowledge the following for funding: Studienstiftung des deutschen Volkes for a studentship (N.K.); the Wellcome Trust (WT 083481 ) (Dundee); the National Institutes of Health Grant ( R01 AI34432 ) (M.A.P.); and the Welch Foundation Grant I-1257 (M.A.P.). M.A.P. holds the Carolyn R. Bacon Professorship in Medical Science and Education.

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.

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.

KW - Ornithine decarboxylase

KW - P2 transporter

KW - Trypanosoma brucei

UR - http://www.scopus.com/inward/record.url?scp=77955428923&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955428923&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2010.06.070

DO - 10.1016/j.bmcl.2010.06.070

M3 - Article

C2 - 20615694

AN - SCOPUS:77955428923

SN - 0960-894X

VL - 20

SP - 4364

EP - 4366

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 15

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this