title: From a cytotoxic agent to the discovery of a novel antimalarial agent.
abstract: A novel cytotoxin 3,5-bis(4-chlorobenzylidene)-1-[4-{2-(4-morpholinyl)ethoxy}phenyl-carbonyl]-4-piperidone hydrochloride 2 demonstrated potent antimalarial properties with IC(50) values of 0.60 and 1.97 μM against the drug sensitive D6 strain and the C235 drug-resistant strain of Plasmodium falciparum. This compound concentrates in red blood cells, lowers glutathione concentrations in erythrocytes and permeates across CACO-2 cells. These data reveal 2 to be a promising lead compound in the quest for novel antimalarial agents.
authors.affiliation: Drug Design and Discovery Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5C9.
authors.forename: Ravi S P
authors.initials: RS
authors.lastname: Singh
authors.forename: Umashankar
authors.initials: U
authors.lastname: Das
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Auschwitz
authors.forename: Susan E
authors.initials: SE
authors.lastname: Leed
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hickman
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Dimmock
authors.forename: Jane
authors.initials: J
authors.lastname: Alcorn
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018938:Caco-2 Cells; D055808:Drug Discovery; D004351:Drug Resistance; D006801:Humans; D020128:Inhibitory Concentration 50; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010881:Piperidones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects
chemical_list: C581884:3,5-bis(4-chlorobenzylidene)-1-(4-(2-(4-morpholinyl)ethoxy)phenyl-carbonyl)-4-piperidone; D000962:Antimalarials; D009025:Morpholines; D010881:Piperidones