title: Kojic acid derived hydroxypyridinone-chloroquine hybrids: synthesis, crystal structure, antiplasmodial activity and β-haematin inhibition.
abstract: Aminochloroquinoline-kojic acid hybrids were synthesized and evaluated for β-haematin inhibition and antiplasmodial activity against drug resistant (K1) and sensitive (3D7) strains of Plasmodium falciparum. Compound 7j was the most potent compound in both strains (IC50(3D7)=0.004 μM; IC50(K1)=0.03 μM) and had the best β-haematin inhibition activity (0.07 IC50 equiv vs 1.91 IC50 equiv for chloroquine). One compound 8c was found to be equipotent in both strains (IC50=0.04 μM).
authors: Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
authors: Warren Andrew
authors: WA
authors: Andayi
authors: Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
authors: Timothy J
authors: TJ
authors: Egan
authors: Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; South African Medical Research Council Drug Discovery & Development Research Unit, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa. Electronic address: Kelly.Chibale@uct.ac.za.
authors: Kelly
authors: K
authors: Chibale
mesh_terms: D000634:Aminoquinolines / Q000737:chemistry*; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D006420:Hemeproteins / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011728:Pyridones / Q000737:chemistry*; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C000595735:2-(((3-(7-chloroquinolin-4-ylamino)propyl)(methyl)amino)methyl)-5-hydroxy-1-methylpyridin-4(1H)-one; C000595734:5-(benzyloxy)-2-((6-(7-chloroquinolin-4-ylamino)hexylamino)methyl)-1-cyclopropylpyridin-4(1H)-one; D000634:Aminoquinolines; D000962:Antimalarials; D006420:Hemeproteins; D011728:Pyridones; D011753:Pyrones; C020753:hemozoin; C011890:kojic acid
keywords: Antiplasmodial; Haematin inhibition; Hybrids; Hydroxypyridinone; Kojic acid