IN-VITRO ANTIMALARIAL ACTIVITY OF CHALCONES AND THEIR DERIVATIVES

A series of chalcones and their derivatives have been synthesized and identified as novel potential antimalarials using both molecular model ing and in vitro testing against the intact parasite. A large number o f chalcones and their derivatives were prepared using one-step Claisen -Schmidt condensations of aldehydes with methyl ketones. These condens ates were screened in vitro against both chloroquine-sensitive and chl oroquine-resistant strains of Plasmodium falciparum and shown to be ac tive at concentrations in the nanomolar range. The most active chalcon e derivative, ,5-dichlorophenyl)-3-(4-quinolinyl)-2-propen-1-one (7), had an IC50 value of 200 nM against both a chloroquine-resistant strai n (W2) and a chloroquine-sensitive strain (D6). The resistance indexes for all compounds were substantially lower than for chloroquine, sugg esting that this series will be active against chloroquine-resistant m alaria. Structure-activity relationships (SAR) of the chalcones in the context of a homology-based model structure of the malaria trophozoit e cysteine protease, the most likely target enzyme, are presented.