Overcoming drug resistance to heme-targeted antimalarials by systematic side chain variation of 7-chloro-4-aminoquinolines.
Systematic variation of the branching and basicity of the side chain of chloroquine yielded a series of new 7-chloro-4-aminoquinoline derivatives exhibiting high in vitro activity against four different strains of P. falciparum. Many of the compounds tested showed excellent potency against chloroquine sensitive and resistant strains. In particular 4b, 5a, 5b, 5d, 17a, and 17b were found to be significantly more potent than chloroquine against the resistant strains Dd2 and FCB.
Yearick
Kimberly
K
Department of Chemistry, Department of Biochemistry and Cellular and Molecular Biology, and Center for Infectious Diseases, Georgetown University, 37th and O Streets, Washington, D.C., USA.
Ekoue-Kovi
Kekeli
K
Iwaniuk
Daniel P
DP
Natarajan
Jayakumar K
JK
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*; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000634:Aminoquinolines; D000962:Antimalarials; C047186:7-chloro-4-aminoquinoline