title: Overcoming drug resistance to heme-targeted antimalarials by systematic side chain variation of 7-chloro-4-aminoquinolines.
abstract: 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.
authors.affiliation: 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.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Yearick
authors.forename: Kekeli
authors.initials: K
authors.lastname: Ekoue-Kovi
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Iwaniuk
authors.forename: Jayakumar K
authors.initials: JK
authors.lastname: Natarajan
authors.forename: John
authors.initials: J
authors.lastname: Alumasa
authors.forename: Angel C
authors.initials: AC
authors.lastname: de Dios
authors.forename: Paul D
authors.initials: PD
authors.lastname: Roepe
authors.forename: Christian
authors.initials: C
authors.lastname: Wolf
mesh_terms: 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
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; C047186:7-chloro-4-aminoquinoline