Sponge-derived natural products lead to new antimalarial

Scientists have discovered a small molecule that suppresses malaria-causing parasites in vitro and in humanized mice by targeting a key parasitic organelle. ( Science 2024, DOI: 10.1126/science.adm7966 ). Isocyanoterpenes are a family of natural products that are found in marine sponges. Many compounds belonging to the family have antibacterial, antifungal, and antimalarial properties. But the compounds are often complex and difficult to synthesize, leading chemists to search for simplified analogs. Scientists found that when they simplified an antimalarial isocyanoterpene compound called kalihinol B, the resulting small molecule—which they dubbed MED6-189—retained kalihinol B’s antimalarial properties. MED6-189 inhibited the growth of normal and antimalarial-resistant Plasmodium falciparum parasites in vitro. The researchers discovered that MED6-189 targets the apicoplast, a parasite-specific organelle wherein fatty acids and other essential molecules are synthesized. Further analyses suggest that the compound may interfere with several molecular pathways essential to the parasite’s survival. Parasites can develop resistance to small-molecule