A medicinal chemistry perspective on 4-aminoquinoline antimalarial drugs.
A broad overview is presented describing the current knowledge and the ongoing research concerning the 4-aminoquinolines (4AQ) as chemotherapeutic antimalarial agents. Included are discussions of mechanism of action, structure activity relationships (SAR), chemistry, metabolism and toxicity and parasite resistance mechanisms. In discussions of SAR, particular emphasis has been given to activity versus chloroquine resistant strains of Plasmodium falciparum. Promising new lead compounds undergoing development are described and an overview of physicochemical properties of chloroquine and amodiaquine analogues is also included.
O'Neill
Paul M
PM
Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L67 7ZD UK. P.M.oneill01@liv.ac.uk
Ward
Stephen A
SA
Berry
Neil G
NG
Jeyadevan
J Prince
JP
Biagini
Giancarlo A
GA
Asadollaly
Egbaleh
E
Park
B Kevin
BK
Bray
Patrick G
PG
D000634:Aminoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000655:Amodiaquine / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002738:Chloroquine / Q000737:chemistry / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000634:Aminoquinolines; D000962:Antimalarials; D000655:Amodiaquine; D002738:Chloroquine; C001920:4-aminoquinoline