Synthesis and activity of some antimalarial bisquinolines.
A new type of bisquinoline antimalarial, in which the basic side chain of chloroquine is retained, has been evaluated. Nine bisamides were prepared from aliphatic diacids with 6-amino- and 8-amino-((4-(diethylamino)-1-methylbutyl)amino)quinoline, and screened against chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro. The resistance indices for all compounds were lower than for chloroquine. The position of attachment and length of the linker chain markedly affected activity. The most active (IC50 = 120 nM against the chloroquine-resistant FAC8 strain) was the -(O)C(CH2)4C(O)- linked 8-amino compound.
Chemistry School, La Trobe University, Bundoora, Victoria, Australia.
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K
Raynes
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Galatis
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Cowman
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Tilley
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Deady
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D002738:Chloroquine / Q000031:analogs & derivatives; D010963:Plasmodium falciparum / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*
D000962:Antimalarials; D011804:Quinolines; D002738:Chloroquine