Synthesis and antimalarial activity of side chain modified 4-aminoquinoline derivatives.
A new series of side-chain modified 4-aminoquinolines have been synthesized and found active against P. falciparum in vitro and P. yoelli in vivo. Compounds 6, 11, 12, and 19 exhibited superior in vitro activity compared to chloroquine. Selected compounds 6, 12, and 19 exhibited significant suppression in the in vivo assay. These analogs form a complex with hematin and inhibit the beta-hematin formation, suggesting that this class of compounds act on a heme polymerization target.
Solomon
V Raja
VR
Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow 226 001, India.
Haq
W
W
Srivastava
Kumkum
K
Puri
Sunil K
SK
Katti
S B
SB
D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006420:Hemeproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051379:Mice; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D010967:Plasmodium yoelii / Q000187:drug effects; D013329:Structure-Activity Relationship
D000634:Aminoquinolines; D000962:Antimalarials; D006420:Hemeproteins; C020753:hemozoin