Biologically active bisbenzylisoquinoline alkaloids from the root bark of Epinetrum villosum

Methanol and water extracts of the root of Epinetrum villosum (Exell) Troupin (Menispermaceae) were found to exhibit antimicrobial and antiplasmodial activities. Investigation of the active methanol fraction led to the isolation of four bisbenzylisoquinoline alkaloids, i.e., cycleanine, cycleanine N-oxide, isochondodendrine and cocsoline. Structures were established by spectroscopic methods. Cocsoline displayed antibacterial and antifungal activities (MIC values of 1000-15.62 and 31.25 μg/ml, respectively). Isochondodendrine was found to have the most potent antiplasmodial activity (IC50 = 0.10 μg/ml), whereas the IC50 on HCT-116 human colon carcinoma cells was 17.5 μg/ml (selectivity index 175). Cycleanine acted against HIV-2 (EC50 = 1.83 μg/ml) but was at least 10-fold less active against HIV-1. Cycleanine N-oxide showed no activity towards all tested microorganisms.