- Synthesis and antimalarial evaluation of novel isocryptolepine derivatives.
Synthesis and antimalarial evaluation of novel isocryptolepine derivatives.
Bioorganic & medicinal chemistry (2011-11-08)
Louise R Whittell, Kevin T Batty, Rina P M Wong, Erin M Bolitho, Simon A Fox, Timothy M E Davis, Paul E Murray
PMID22055713
摘要
A series of mono- and di-substituted analogues of isocryptolepine have been synthesized and evaluated for in vitro antimalarial activity against chloroquine sensitive (3D7) and resistant (W2mef) Plasmodium falciparum and for cytotoxicity (3T3 cells). Di-halogenated compounds were the most potent derivatives and 8-bromo-2-chloroisocryptolepine displayed the highest selectivity index (106; the ratio of cytotoxicity (IC(50)=9005 nM) to antimalarial activity (IC(50)=85 nM)). Our evaluation of novel isocryptolepine compounds has demonstrated that di-halogenated derivatives are promising antimalarial lead compounds.