title: Quinolin-4(1H)-imines are potent antiplasmodial drugs targeting the liver stage of malaria.
abstract: We present a novel series of quinolin-4(1H)-imines as dual-stage antiplasmodials, several-fold more active than primaquine in vitro against Plasmodium berghei liver stage. Among those, compounds 5g and 5k presented low nanomolar IC50 values. The compounds are metabolically stable and modulate several drug targets. These results emphasize the value of quinolin-4(1H)-imines as a new chemotype and their suitable properties for further drug development.
authors.affiliation: Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Avenida Prof. Gama Pinto, 1649-019 Lisbon, Portugal. tiago.rodrigues@pharma.ethz.ch
authors.forename: Tiago
authors.initials: T
authors.lastname: Rodrigues
authors.forename: Filipa P
authors.initials: FP
authors.lastname: da Cruz
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Lafuente-Monasterio
authors.forename: Daniel
authors.initials: D
authors.lastname: Gonçalves
authors.forename: Ana S
authors.initials: AS
authors.lastname: Ressurreição
authors.forename: Ana R
authors.initials: AR
authors.lastname: Sitoe
authors.forename: Maria R
authors.initials: MR
authors.lastname: Bronze
authors.forename: Jiri
authors.initials: J
authors.lastname: Gut
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
authors.forename: Maria M
authors.initials: MM
authors.lastname: Mota
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Miguel
authors.initials: M
authors.lastname: Prudêncio
authors.forename: Francisco-Javier
authors.initials: FJ
authors.lastname: Gamo
authors.forename: Francisca
authors.initials: F
authors.lastname: Lopes
authors.forename: Rui
authors.initials: R
authors.lastname: Moreira
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D007097:Imines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000469:parasitology; D008288:Malaria / Q000188:drug therapy*; D021261:Parasitic Sensitivity Tests; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D007097:Imines; D011804:Quinolines