Antimalarial activity: the search for marine-derived natural products with selective antimalarial activity

In this short review, an approach to the isolation of potential antimalarial agents and lead compounds is outlined. A discussion of organism collection, followed by a description of biological testing and isolation methodologies, is also given. For two organisms, details of their secondary metabolite chemistry are reported. From one of these, Laurencia papillosa, the two aromatic compounds p-hydroxybenzaldehyde (1) and p-methoxybenzyl alcohol (2) were isolated. From the other, the tropical marine sponge Cymbastela hooperi, 15 diterpenes (3-17), which contain isonitrile, isothiocyanate, and isocyanate functionalities, are reported. Together with the diterpenes, three sesquiterpene hydrocarbons, 18-20, and the thiol, 21, were obtained. All structures were established by spectroscopic methods, particularly 1H-1H and 1H-13C shift-correlated 2D NMR spectroscopy and accurate mass measurement (HREIMS). The majority of isolates demonstrate significant and selective in vitro antimalarial activity. For compounds 4-17 a brief description of their possible structure-activity relationships is provided.