Novel short chain chloroquine analogues retain activity against chloroquine resistant K1 Plasmodium falciparum.
A series of short chain chloroquine (CQ) derivatives have been synthesized in one step from readily available starting materials. The diethylamine function of CQ is replaced by shorter alkylamine groups (4-9) containing secondary or tertiary terminal nitrogens. Some of these derivatives are significantly more potent than CQ against a CQ resistant strain of Plasmodium falciparum in vitro. We conclude that the ability to accumulate at higher concentrations within the food vacuole of the parasite is an important parameter that dictates their potency against CQ sensitive and the chloroquine resistant K1 P. falciparum.
Stocks
Paul A
PA
Department of Chemistry, The University of Liverpool, United Kingdom.
Raynes
Kaylene J
KJ
Bray
Patrick G
PG
Park
B Kevin
BK
O'Neill
Paul M
PM
Ward
Stephen A
SA
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D002738:Chloroquine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D004351:Drug Resistance; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006427:Hemin / Q000378:metabolism; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000962:Antimalarials; D006427:Hemin; D002738:Chloroquine