title: Synthesis and in vitro and in vivo antimalarial activity of N1-(7-chloro-4-quinolyl)-1,4-bis(3-aminopropyl)piperazine derivatives.
abstract: Three series of monoquinolines consisting of a 1,4-bis(3-aminopropyl)piperazine linker and a large variety of terminal groups were synthesized. Our aim was to prove that in related bisquinoline, it is the second quinoline moiety that is responsible for cytotoxicity and that it is not an absolute requirement for overcoming resistance to chloroquine (CQ). Eleven compounds displayed a higher selectivity index (ratio CC50/IC50 activity) than CQ, and one of them cured mice infected by Plasmodium berghei.
authors.affiliation: UMR 8525 CNRS, Université de Lille II, Institut de Biologie et Institut Pasteur de Lille, 1 rue du Professeur Calmette, B.P. 447, 59021 Lille Cedex, France.
authors.forename: Adina
authors.initials: A
authors.lastname: Ryckebusch
authors.forename: Rébecca
authors.initials: R
authors.lastname: Deprez-Poulain
authors.forename: Louis
authors.initials: L
authors.lastname: Maes
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Debreu-Fontaine
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mouray
authors.forename: Philippe
authors.initials: P
authors.lastname: Grellier
authors.forename: Christian
authors.initials: C
authors.lastname: Sergheraert
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000962:Antimalarials; D000970:Antineoplastic Agents; D010879:Piperazines; D011804:Quinolines; D002738:Chloroquine