Synthesis and antimalarial activity of new chloroquine analogues carrying a multifunctional linear side chain.
We report the synthesis and in vitro antimalarial activity of several new 4-amino- and 4-alkoxy-7-chloroquinolines carrying a linear dibasic side chain. Many of these chloroquine analogues have submicromolar antimalarial activity versus HB3 (chloroquine sensitive) and Dd2 (chloroquine resistant strain of Plasmodium falciparum) and low resistance indices were obtained in most cases. Importantly, compounds 11-15 and 24 proved to be more potent against Dd2 than chloroquine. Branching of the side chain structure proved detrimental to the activity against the CQR strain.
Iwaniuk
Daniel P
DP
Department of Chemistry, Georgetown University, 37th and 'O' Streets, Washington, DC 22057, United States.
Whetmore
Eric D
ED
Rosa
Nicholas
N
Ekoue-Kovi
Kekeli
K
Alumasa
John
J
de Dios
Angel C
AC
Roepe
Paul D
PD
Wolf
Christian
C
D000634:Aminoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002738:Chloroquine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000188:drug therapy*; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*
D000634:Aminoquinolines; D000962:Antimalarials; D002738:Chloroquine; C001920:4-aminoquinoline
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