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Inspired by the discovery of the antimalarial drug artemisinin from a traditional Chinese medicine (TCM), a natural product library of 44 lindenane-type sesquiterpenoids was assessed for activities against the Dd2 chloroquine-resistant strain of the malaria parasite Plasmodium falciparum. These compounds were mainly isolated from plants of the Chloranthus genus, many species of which are named "Sikuaiwa" in TCM and have long been used to treat malaria. The compounds consisted of 41 sesquiterpenoid dimers and three monomers, including the 12 new dimers 1-12 isolated from Chloranthus fortunei. The results showed that 16 dimers exhibited potent antiplasmodial activities (&lt;100 nM); in particular, compounds 1, 14, and 19 exhibited low nanomolar activities with IC 50 values ranging from 1 to 7 nM, which is comparable to the potency of artemisinin, and selectivity index values toward mammalian cells greater than 500. A comprehensive structure-activity relationship study indicated that three functional groups are essential and two motifs can be modified.

journal of natural products

Nanomolar Antimalarial Agents against Chloroquine-Resistant <i>Plasmodium falciparum</i> from Medicinal Plants and Their Structure–Activity Relationships

Nanomolar Antimalarial Agents against Chloroquine-Resistant Plasmodium falciparum from Medicinal Plants and Their Structure–Activity Relationships