Evaluation of Jatropha isabelli natural products and their synthetic analogs as potential antimalarial therapeutic agents

• We have identified new class of antimalarial compounds.
• We have synthesized a focused compound library based on the lead natural product, jatrophone.
• Compounds 25 and 32 were active against the 3D7 and K1 strains in mammalian cell lines, without cytotoxicity.

Protozoal diseases such as malaria are a leading world health concern. We screened a library of fractionated natural products to identify new potential therapeutic leads and discovered that jatrophone (a product of Jatropha isabelli) exerts significant activity against Plasmodium falciparum strains 3D7 and K1. A focused jatrophone-scaffold library was synthesized to evaluate jatrophone's mode of action and identify more selective analogs. Compounds 25 and 32 of this natural product–inspired compound library exhibited micromolar EC50 values against strains 3D7 and K1, thus providing a new antimalarial molecular scaffold. Our report describes an efficient derivatization approach used to evaluate the structure–activity relationship of jatrophone analogs in search of potential new antimalarial agents.

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