Targeted delivery of compounds to Trypanosoma brucei using the melamine motif

Constance Chollet, Alessandro Baliani, Pui Ee Wong, Michael P. Barrett, Ian H. Gilbert

    Research output: Contribution to journalArticle

    31 Citations (Scopus)

    Abstract

    There is an urgent need for the development of new drugs for the treatment of human African trypanosomiasis. The causative organism, Trypanosoma brucei, has been shown to have some unusual plasma membrane transporters, in particular the P2 aminopurine transporter and related permeases, which have been used for the selective targeting of trypanocidal compounds to the organism. In this paper, we report the addition of melamine-based P2-targeting motifs to three different classes of compound in order to try and improve activity through increased selective uptake. The classes reported here are fluoroquinolones, difluoromethylornithine and artesunate derivatives. (C) 2009 Elsevier Ltd. All rights reserved.

    Original languageEnglish
    Pages (from-to)2512-2523
    Number of pages12
    JournalBioorganic & Medicinal Chemistry
    Volume17
    Issue number6
    DOIs
    Publication statusPublished - 15 Mar 2009

    Keywords

    • Trypanosoma brucei
    • Delivery
    • Melamine
    • Eflornithine
    • Fluoroquinolones
    • UNUSUAL ADENOSINE TRANSPORTER
    • AFRICAN TRYPANOSOMES
    • ANTITRYPANOSOMAL ACTIVITY
    • CROSS-RESISTANCE
    • DIAMIDINE DRUGS
    • ARTEMISININS
    • NITROHETEROCYCLES
    • FLUOROQUINOLONES
    • TOPOISOMERASES
    • CHEMOTHERAPY

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