Synthesis and antimalarial evaluation of a series of piperazinyl flavones.
A series of 27 flavonoid derivatives containing a piperazinyl chain have been synthesized and tested for their antiplasmodial activity. Diverse substitution patterns on piperazinyl and flavone moieties were examined and found to affect the activity differently. The most active compounds, which have a 2,3,4-trimethoxybenzylpiperazinyl chain attached to the flavone at the 7-phenol group, showed in vitro activity against chloroquine-sensitive (Thai) and -resistant (FcB1,K1) Plasmodium falciparum strains in the micromolar to submicromolar range. One of them was active when given orally in a Plasmodium yoelii nigeriensis infected mouse model.
Auffret
Gwenola
G
Laboratoire de Pharmacognosie, (Univ. Paris-Sud, BIOCIS, UMR-8076 CNRS), Faculté de Pharmacie, av. J.B. Clément, 92296 Châtenay-Malabry Cedex, France.
Labaied
Mehdi
M
Frappier
François
F
Rasoanaivo
Philippe
P
Grellier
Philippe
P
Lewin
Guy
G
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D047309:Flavones / Q000138:chemical synthesis* / Q000494:pharmacology*; D019450:Genes, MDR; D006801:Humans; D007202:Indicators and Reagents; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D051379:Mice; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship
D000962:Antimalarials; D047309:Flavones; D007202:Indicators and Reagents; D010879:Piperazines; D002738:Chloroquine