Synthesis and antimalarial evaluation of new N1-(7-chloro-4-quinolyl)-1,4-bis(3-aminopropyl)piperazine derivatives.
Synthesis and evaluation of the activity of new N(1)-(7-chloro-4-quinolyl)-1,4-bis(3-aminopropyl)piperazine derivatives against a chloroquine-resistant strain of Plasmodium falciparum are described. Selectivity indices were improved for two compounds versus the lead 1, the bis-cyclopropylmethyl derivative, thus increasing the therapeutic interest of our family. As our previous studies conducted on the mode of action of our compounds made us hypothesize the existence of original mechanisms and/or original targets, terminal amino derivatives can be considered as promising tools further mechanistical studies, as probes for affinity chromatography.
Ryckebusch
Adina
A
Institut de Biologie et Institut Pasteur de Lille-UMR CNRS 8525-Université de Lille II 1 rue du Professeur Calmette, B.P. 447, 59021 Lille, France.
Debreu-Fontaine
Marie-Ange
MA
Mouray
Elisabeth
E
Grellier
Philippe
P
Sergheraert
Christian
C
Melnyk
Patricia
P
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D002846:Chromatography, Affinity; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*
D000962:Antimalarials; D010879:Piperazines; D002738:Chloroquine