title: Novel squaramides with in vitro liver stage antiplasmodial activity.
abstract: A structure-activity relationship study was performed with ten 8-aminoquinoline-squaramides compounds active against liver stage malaria parasites, using human hepatoma cells (Huh7) infected by Plasmodium berghei parasites. In addition, their blood-schizontocidal activity was assessed against chloroquine-resistant W2 strain Plasmodium falciparum. Compound 3 was 7.3-fold more potent than the positive control primaquine against liver-stage parasites, illustrating the importance of the squarate moiety to activity.
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Carlos J A
authors.initials: CJ
authors.lastname: Ribeiro
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Margarida
authors.initials: M
authors.lastname: Espadinha
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Machado
authors.affiliation: Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA 94143, USA.
authors.forename: Jiri
authors.initials: J
authors.lastname: Gut
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Lídia M
authors.initials: LM
authors.lastname: Gonçalves
authors.affiliation: Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA 94143, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal.
authors.forename: Miguel
authors.initials: M
authors.lastname: Prudêncio
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Moreira
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal. Electronic address: mariasantos@ff.ulisboa.pt.
authors.forename: Maria M M
authors.initials: MM
authors.lastname: Santos
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D008099:Liver / Q000469:parasitology*; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology*; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011803:Quinine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000981:Antiprotozoal Agents; C000609819:squaramide; D011803:Quinine
keywords: 8-Aminoquinoline; Antiplasmodial activity; Liver stage; Malaria; Squaramide