title: Syntheses and in Vitro Antiplasmodial Activity of Aminoalkylated Chalcones and Analogues.
abstract: A series of readily synthesized and inexpensive aminoalkylated chalcones and diarylpropane analogues (1-55) were synthesized and tested against chloroquinone-sensitive (D10 and NF54) and -resistant (Dd2 and K1) strains of Plasmodium falciparum. Hydrogenation of the enone to a diarylpropane moiety increased antiplasmodial bioactivity significantly. The influence of the structure of the amine moiety, A-ring substituents, propyl vs ethyl linker, and chloride salt formation on further enhancing antiplasmodial activity was investigated. Several compounds have IC₅₀ values similar to or better than chloroquine (CQ). The most active compound (26) had an IC₅₀ value of 0.01 μM. No signs of resistance were detected, as can be expected from compounds with structures unrelated to CQ and other currently used antimalarial drugs. Toxicity tests (in vitro CHO cell assay) gave high SI indices.
authors.forename: Anke
authors.initials: A
authors.lastname: Wilhelm
authors.forename: Pravin
authors.initials: P
authors.lastname: Kendrekar
authors.forename: Anwar E M
authors.initials: AE
authors.lastname: Noreljaleel
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , Cape Town, South Africa.
authors.forename: Efrem T
authors.initials: ET
authors.lastname: Abay
authors.forename: Susan L
authors.initials: SL
authors.lastname: Bonnet
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , Cape Town, South Africa.
authors.forename: Lubbe
authors.initials: L
authors.lastname: Wiesner
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , Cape Town, South Africa.
authors.forename: Carmen
authors.initials: C
authors.lastname: de Kock
authors.affiliation: PAREXEL International Clinical Research Organization , Private Bag X09, Brandhof 9324, Bloemfontein 339, South Africa.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Swart
authors.forename: Jan Hendrik
authors.initials: JH
authors.lastname: van der Westhuizen
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D006224:Cricetinae; D003412:Cricetulus; D004351:Drug Resistance / Q000187:drug effects; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D047188:Chalcones; D002738:Chloroquine