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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.

SUBMITTER: Klee N

PROVIDER: S-EPMC2935964 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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

Klee Nina N Wong Pui Ee PE Baragaña Beatriz B Mazouni Farah El FE Phillips Margaret A MA Barrett Michael P MP Gilbert Ian H IH

Bioorganic & medicinal chemistry letters 20100617 15

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 her ...[more]

PMID: 20615694

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