title: Design, Synthesis, and Evaluation of Novel Ferroquine and Phenylequine Analogues as Potential Antiplasmodial Agents.
abstract: 7-Chloroquinoline-based antimalarial drugs are effective in the inhibition of hemozoin formation in the food vacuole of the Plasmodium parasite, the causative agent of malaria. We synthesized five series of ferroquine (FQ) and phenylequine (PQ) derivatives, which display good in vitro efficacy toward both the chloroquine-sensitive (CQS) NF54 (IC50 : 4.2 nm) and chloroquine-resistant (CQR) Dd2 (IC50 : 33.7 nm) strains of P. falciparum. Several compounds were found to have good inhibitory activity against β-hematin formation in an NP-40 detergent assay, with IC50 values ranging between 10.4 and 19.2 μm.
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland, 7602, South Africa.
authors.forename: Leon
authors.initials: L
authors.lastname: Jacobs
authors.affiliation: Department of Pharmacology, University of Cape Town, Private Bag X2, Rondebosch, Cape Town, 7700, South Africa.
authors.forename: Carmen
authors.initials: C
authors.lastname: de Kock
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland, 7602, South Africa.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: de Villiers
authors.affiliation: Department of Pharmacology, University of Cape Town, Private Bag X2, Rondebosch, Cape Town, 7700, South Africa.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Smith
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland, 7602, South Africa.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Smith
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland, 7602, South Africa.
authors.forename: Willem A L
authors.initials: WA
authors.lastname: van Otterlo
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland, 7602, South Africa. mblackie@sun.ac.za.
authors.forename: Margaret A L
authors.initials: MA
authors.lastname: Blackie
mesh_terms: D000634:Aminoquinolines / Q000737:chemistry* / Q000494:pharmacology; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002738:Chloroquine / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D015195:Drug Design; D004351:Drug Resistance / Q000187:drug effects; D005296:Ferrous Compounds / Q000737:chemistry* / Q000494:pharmacology; D006420:Hemeproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D020128:Inhibitory Concentration 50; D000075163:Metallocenes; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D017830:Octoxynol; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D005296:Ferrous Compounds; D006420:Hemeproteins; D000075163:Metallocenes; C020753:hemozoin; D011092:Polyethylene Glycols; D002738:Chloroquine; C479230:ferroquine; D017830:Octoxynol; C010615:Nonidet P-40
keywords: ferroquine; malaria; oxalamide; phenylequine; β-hematin