Synthesis and antimalarial evaluation of novel isocryptolepine derivatives

L.R. Whittell, K.T. Batty, R.P.M. Wong, E.M. Bolitho, Simon Fox, Timothy Davis, P.E. Murray

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    Abstract

    A series of mono- and di-substituted analogues of isocryptolepine have been synthesized and evaluated for in vitro antimalarial activity against chloroquine sensitive (3D7) and resistant (W2mef) Plasmodium falciparum and for cytotoxicity (3T3 cells). Di-halogenated compounds were the most potent derivatives and 8-bromo-2-chloroisocryptolepine displayed the highest selectivity index (106; the ratio of cytotoxicity (IC 50 = 9005 nM) to antimalarial activity (IC 50 = 85 nM)). Our evaluation of novel isocryptolepine compounds has demonstrated that di-halogenated derivatives are promising antimalarial lead compounds. © 2011 Elsevier Ltd. All rights reserved.
    Original languageEnglish
    Pages (from-to)7519-7525
    JournalBioorganic and Medicinal Chemistry
    Volume19
    Issue number24
    DOIs
    Publication statusPublished - 2011

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    Antimalarials
    Cytotoxicity
    Derivatives
    Lead compounds
    3T3 Cells
    Chloroquine
    Plasmodium falciparum
    isocryptolepine

    Cite this

    Whittell, L.R. ; Batty, K.T. ; Wong, R.P.M. ; Bolitho, E.M. ; Fox, Simon ; Davis, Timothy ; Murray, P.E. / Synthesis and antimalarial evaluation of novel isocryptolepine derivatives. In: Bioorganic and Medicinal Chemistry. 2011 ; Vol. 19, No. 24. pp. 7519-7525.
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    Synthesis and antimalarial evaluation of novel isocryptolepine derivatives. / Whittell, L.R.; Batty, K.T.; Wong, R.P.M.; Bolitho, E.M.; Fox, Simon; Davis, Timothy; Murray, P.E.

    In: Bioorganic and Medicinal Chemistry, Vol. 19, No. 24, 2011, p. 7519-7525.

    Research output: Contribution to journalArticle

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    AU - Whittell, L.R.

    AU - Batty, K.T.

    AU - Wong, R.P.M.

    AU - Bolitho, E.M.

    AU - Fox, Simon

    AU - Davis, Timothy

    AU - Murray, P.E.

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    AB - A series of mono- and di-substituted analogues of isocryptolepine have been synthesized and evaluated for in vitro antimalarial activity against chloroquine sensitive (3D7) and resistant (W2mef) Plasmodium falciparum and for cytotoxicity (3T3 cells). Di-halogenated compounds were the most potent derivatives and 8-bromo-2-chloroisocryptolepine displayed the highest selectivity index (106; the ratio of cytotoxicity (IC 50 = 9005 nM) to antimalarial activity (IC 50 = 85 nM)). Our evaluation of novel isocryptolepine compounds has demonstrated that di-halogenated derivatives are promising antimalarial lead compounds. © 2011 Elsevier Ltd. All rights reserved.

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