title: Synthesis and antimalarial evaluation of new 1,4-bis(3-aminopropyl)piperazine derivatives.
abstract: Synthesis and evaluation of the activity of a new family of 1,4-bis(3-aminopropyl)piperazine derivatives against a chloroquine-resistant strain of Plasmodium falciparum, and as inhibitors of beta-hematin formation, are described. The highest antimalarial activities were obtained for compounds displaying the highest predicted vacuolar accumulation ratios and the best potencies as inhibitors of beta-hematin formation. The most potent compound displayed an activity 3-fold better than chloroquine for a comparable selectivity index upon MRC-5 cells. Therefore, in this series, the replacement of the 7-chloroquinoline group can constitute a strong rationale for further investigation.
authors.affiliation: Institut de Biologie et Institut Pasteur de Lille, UMR 8525 CNRS, Université de Lille II, 1 rue du Professeur Calmette, B.P. 447, 59021 Lille, France.
authors.forename: Adina
authors.initials: A
authors.lastname: Ryckebusch
authors.forename: Rébecca
authors.initials: R
authors.lastname: Deprez-Poulain
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Debreu-Fontaine
authors.forename: Richard
authors.initials: R
authors.lastname: Vandaele
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: D000465:Algorithms; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance; D006420:Hemeproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006801:Humans; D007202:Indicators and Reagents; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship; D014617:Vacuoles / Q000187:drug effects
chemical_list: D000962:Antimalarials; D006420:Hemeproteins; D007202:Indicators and Reagents; D010879:Piperazines; C020753:hemozoin; C486841:1,4-bis(3-aminopropyl)piperazine; D002738:Chloroquine