ISHS Acta Horticulturae 677: III WOCMAP Congress on Medicinal and Aromatic Plants - Volume 3: Perspectives in Natural Product Chemistry
SYNTHESIS, CYTOTOXICITY AND ANTIPLASMODIAL ACTIVITY OF NEOCRYPTOLEPINE DERIVATIVES |
| Authors: | S. Van Miert, T. Jonckers, L. Maes, A. Vlietinck |
| Keywords: | Cryptolepis sanguinolenta, Periplocaceae, cryptolepine, neocryptolepine, Plasmodium, malaria |
| Abstract:
Based on the original lead neocryptolepine, an alkaloid from Cryptolepis sanguinolenta, a series of substituted derivatives was prepared. All compounds were evaluated for their activity against chloroquine-resistant Plasmodium falciparum strains, and for their cytotoxicity on human MRC-5 cells. Mechanisms of action were investigated by testing inhibition of  -haematin formation and DNA interactions (DNA-methylgreen assay). Some neocryptolepine derivatives with a higher antiplasmodial activity and a lower cytotoxicity than the original lead have been obtained.
This selective antiplasmodial activity was associated with inhibition of -haematin formation. 2-Bromoneocryptolepine was the most selective compound with an IC50 value against chloroquine-resistant P. falciparum of 4.0 µM in the absence of cytotoxicity (LC50 < 32 µM). This compound was considered as the most promising lead from the present work for new antimalarial agents.
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