Antimalarial activity of 4-(5-trifluoromethyl-1H-pyrazol-1-yl)-chloroquine analogues

Abstract

The antimalarial activity of chloroquine-pyrazole analogues, synthesized from the reaction of 1,1,1-trifluoro-4-methoxy-3-alken-2-ones with 4-hydrazino-7-chloroquinoline, has been evaluated in vitro against a chloroquine resistant Plasmodium falciparumclone. Parasite growth in the presence of the test drugs was measured by incorporation of [3H] hypoxanthine in compar-ison to controls with no drugs. All but one of the eight (4,5-dihydropyrazol-1-yl) chloroquine 2derivatives tested showed a significant activity in vitro, thus, are a promising new class of antimalarials. The three most active ones were also tested in vivo against Plasmodium bergheiin mice. However, the (pyrazol-1-yl) chloroquine 3derivatives were mostly inactive, suggesting that the aromatic functionality of the pyrazole ring was critica