The discovery, synthesis and antimalarial evaluation of natural product-based polyamine alkaloids

Bioassay-guided fractionation of an antimalarial extract derived from the fungus Ramaria subaurantiaca afforded the known polyamine alkaloid, pistillarin. Nine pistillarin analogues were synthesised via EDC-mediated chemistry and these compounds along with the previously reported natural product polyamines, ianthelliformisamines A–C and spermatinamine, were evaluated against Plasmodium falciparum (3D7) parasites and a normal human cell line to determine parasite-specific activity. Spermatinamine (IC50 0.23 μM) and pistillarin (IC50 1.9 μM) were the two most potent antimalarials identified during these studies.

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