SYNTHESIS, CYTOTOXICITY AND ANTIPLASMODIAL ACTIVITY OF NEOCRYPTOLEPINE DERIVATIVES

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.

III WOCMAP Congress on Medicinal and Aromatic Plants – Volume 3: Perspectives in Natural Product Chemistry

S. Van Miert, T. Jonckers, L. Maes, A. Vlietinck

Cryptolepis sanguinolenta, Periplocaceae, cryptolepine, neocryptolepine, Plasmodium, malaria

https://doi.org/10.17660/ActaHortic.2005.677.12