Discovery, Synthesis and Antimalarial Evaluation of Natural Product-based Polyamines

V Choomuenwai; BD Schwartz; KD Beattie; KT Andrews; S Khokhar; RA Davis

doi:10.1055/s-0033-1348550

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Planta Med 2013; 79 - PA2
DOI: 10.1055/s-0033-1348550

Discovery, Synthesis and Antimalarial Evaluation of Natural Product-based Polyamines

V Choomuenwai ¹, BD Schwartz ¹, KD Beattie ¹, KT Andrews ¹, S Khokhar ¹, RA Davis ¹

¹Eskitis Institute, Griffith University, Brisbane, QLD 4111, Australia

Congress Abstract

Bioassay-guided fractionation of an antimalarial organic extract derived from the Australian mushroom Ramaria subaurantica resulted in the isolation of the known spermidine-based alkaloid, pistillarin (1). This molecule was shown to inhibit a chloroquine-sensitive Plasmodium falciparum (3D7) line with an IC₅₀ value of 1.9µM, and displayed low cytotoxicity against neonatal foreskin fibroblast (NFF) cells with an IC₅₀ > 100µM. Substructure searching of an in-house compound library using the spermidine fragment found in 1 identified four other related and previously isolated polyamines, ianthelliformisamines A-C, and spermatinamine that warranted antimalarial investigation. Concomitantly, a small library of pistillarin analogues was synthesized and all compounds were tested in vitro against P. falciparum (3D7) parasites. The synthesis and structure activity relationships of this polyamine alkaloid library will be presented.