Drug screening for antimalarials uses heme biocrystallization inhibition methods as an alternative to parasite cultures, but they involve complex processes and cannot detect artemisinin-like molecules. The described method detects heme-binding compounds by mass spectrometry, using dissociation of the drug-heme adducts to evaluate putative antiplasmodial activity. Applied to a chemical library, it showed a good hit-to-lead ratio and is an efficient early stage screening for complex mixtures like natural extracts.

We here describe the preparation of a series of hybrid molecules containing a combretastatin A-4 moiety and a pironetin analogue fragment. The cytotoxic activities of these compounds have been measured. Relations between structure and cytotoxicity are discussed. Some of the tested compounds showed cytotoxicity values of the same order of magnitude as the parental molecules, combretastatin A-4 and pironetin, and were less toxic than the latter for normal cells.  The normal vs. tumoral cytotoxicity ratio of some of the tested compounds are higher than in the case of the parental molecules, that is, they are safer than the latter compounds.

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