Semi-synthesis of bioactive fluorescent analogues of the cytotoxic marine alkaloid discorhabdin C

Semi-synthetic N-13 alkylated analogues of the cytotoxic marine alkaloid discorhabdin C have been found to exhibit cytotoxicity towards tumour cell lines at comparable levels to that of the natural product. Incorporation of an ethylenediamine linker facilitated the synthesis of a variety of fluorophore-labelled probes, of which dansyl analogue 20 exhibited biological activity, providing a tool for mechanism of action and cellular localization studies. An alternative probe design was also exemplified, whereby a bioactive alkyne-terminated analogue (24) was found to undergo Huisgen 1,3-dipolar cycloaddition ‘click’ reactions with fluorescent azides, enabling studies directed towards activity-based protein profiling.

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