title: Investigation into novel thiophene- and furan-based 4-amino-7-chloroquinolines afforded antimalarials that cure mice.
abstract: We herein report the design and synthesis of a novel series of thiophene- and furan-based aminoquinoline derivatives which were found to be potent antimalarials and inhibitors of β-hematin polymerization. Tested compounds were 3-71 times more potent in vitro than CQ against chloroquine-resistant (CQR) W2 strain with benzonitrile 30 being as active as mefloquine (MFQ), and almost all synthesized aminoquinolines (22/27) were more potent than MFQ against multidrug-resistant (MDR) strain C235. In vivo experiments revealed that compound 28 showed clearance with recrudescence at 40 mg/kg/day, while 5/5 mice survived in Thompson test at 160 mg/kg/day.
authors: Faculty of Chemistry, University of Belgrade, Studentski trg 16, PO Box 51, 11158 Belgrade, Serbia.
authors: Igor M
authors: IM
authors: Opsenica
authors: Faculty of Chemistry, University of Belgrade, Studentski trg 16, PO Box 51, 11158 Belgrade, Serbia.
authors: Tatjana Ž
authors: TŽ
authors: Verbić
authors: Faculty of Chemistry, University of Belgrade, Studentski trg 16, PO Box 51, 11158 Belgrade, Serbia.
authors: Mikloš
authors: M
authors: Tot
authors: Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD 20910, United States.
authors: Richard J
authors: RJ
authors: Sciotti
authors: Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD 20910, United States.
authors: Brandon S
authors: BS
authors: Pybus
authors: Institute for Medical Research, University of Belgrade, Dr. Subotića 4, 11129 Belgrade, Serbia.
authors: Olgica
authors: O
authors: Djurković-Djaković
authors: Institute for Medical Research, University of Belgrade, Dr. Subotića 4, 11129 Belgrade, Serbia.
authors: Ksenija
authors: K
authors: Slavić
authors: Faculty of Chemistry, University of Belgrade, Studentski trg 16, PO Box 51, 11158 Belgrade, Serbia. Electronic address: bsolaja@chem.bg.ac.rs.
authors: Bogdan A
authors: BA
authors: Šolaja
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010962:Plasmodium berghei / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D005663:Furans; D013876:Thiophenes; C039281:furan
keywords: Aminoquinoline inhibitors; Chemotherapy; Cytotoxicity; Furan; Malaria; P. berghei; Thiophene; β-Hematin polymerization inhibitors