Bioassay-Guided Isolation and Identification of Antiplasmodial Compounds from the Stem Bark of Clausena excavata

Clausena excavata is a medicinal plant widely distributed in Southeast Asia. It is used for a variety of indications, including to treat malaria. In our present study, a phytochemical study of the methanol extract from the stem bark of C. excavata led to the isolation of five pyranocoumarins, nordentatin (1), dentatin (2), kinocoumarin (3), clausarin (4), and clausenidin (5), and a coumarin, 8-hydroxy-3″,4″-dihydrocapnolactone-2′,3′-diol (6). The isolation of compound 6 from C. excavata and the antiplasmodial activities against a multidrug-resistant K1 strain of Plasmodium falciparum of 1, 3, and 5 were reported for the first time. Compounds 3 and 4 exhibited potent antiplasmodial activities with EC ₅₀values of 1.10 and 0.58 μM, respectively, while 1 and 5 had EC ₅₀values of 5.62 and 7.15 μM, respectively. A prenyl group attached to the C-3 or C-12 position on the pyranocoumarin ring probably plays an important role on the activity. A hydroxyl group at the C-10 position is also likely to enhance the activity.