title: Investigating the activity of quinine analogues versus chloroquine resistant Plasmodium falciparum.
abstract: Plasmodium falciparum, the deadliest malarial parasite species, has developed resistance against nearly all man-made antimalarial drugs within the past century. However, quinine (QN), the first antimalarial drug, remains efficacious worldwide. Some chloroquine resistant (CQR) P. falciparum strains or isolates show mild cross resistance to QN, but many do not. Further optimization of QN may provide a well-tolerated therapy with improved activity versus CQR malaria. Thus, using the Heck reaction, we have pursued a structure-activity relationship study, including vinyl group modifications of QN. Certain derivatives show good antiplasmodial activity in QN-resistant and QN-sensitive strains, with lower IC(50) values relative to QN.
authors.affiliation: Department of Chemistry and Biochemistry, University of North Carolina, Wilmington, Dobo Hall, 601 S. College Road, Wilmington, NC 28403, USA.
authors.forename: Theresa
authors.initials: T
authors.lastname: Dinio
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Gorka
authors.forename: Andrew
authors.initials: A
authors.lastname: McGinniss
authors.forename: Paul D
authors.initials: PD
authors.lastname: Roepe
authors.forename: Jeremy B
authors.initials: JB
authors.lastname: Morgan
mesh_terms: D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D002930:Cinchona Alkaloids / Q000737:chemistry; D004351:Drug Resistance / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects*; D011803:Quinine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D002930:Cinchona Alkaloids; D002738:Chloroquine; D011803:Quinine