Application of multi-component reactions to antimalarial drug discovery. Part 1: Parallel synthesis and antiplasmodial activity of new 4-aminoquinoline Ugi adducts.
The synthesis of a new class of Ugi adducts incorporating the 4-aminoquinoline moiety is described. The novel compounds are active against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum with the best compound showing an IC(50) value of 73 nM against a resistant K1 strain.
Musonda
Chitalu C
CC
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
Taylor
Dale
D
Lehman
Julie
J
Gut
Jiri
J
Rosenthal
Philip J
PJ
Chibale
Kelly
K
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002738:Chloroquine / Q000737:chemistry; D015767:Mefloquine / Q000737:chemistry; D008968:Molecular Conformation; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects*; D011803:Quinine / Q000737:chemistry; D013329:Structure-Activity Relationship
D000962:Antimalarials; D002738:Chloroquine; D011803:Quinine; D015767:Mefloquine