In vitro and in vivo antimalarial activity of derivatives of 1,10-phenanthroline framework.
A series of trisubstituted 1,10-phenanthrolines was prepared. These compounds exhibited mild to high biological activities in vitro both toward chloroquino-resistant FcB1-Columbia and FcM29-Cameron strains and Nigerian chloroquino-sensitive strain of Plasmodium falciparum. Cytotoxicity of the most active compounds was estimated showing that one compound (10) exhibited a selective activity against malaria parasite (selectivity indexes of 52 and 144). Antiplasmodial activity of this derivative was optimized by N-10 alkylation and the phenanthrolinium salt (15) submitted to an in vivo study using mice infected by P. vinckei petteri showing an ED50 of 7.86 mg/kg/day.
Yapi
Ange-Désiré
AD
Laboratoire de Chimie Thérapeutique, Faculté de Pharmacie, Université de Côte d'Ivoire, Abidjan, Côte d'Ivoire.
Valentin
Alexis
A
Chezal
Jean-Michel
JM
Chavignon
Olivier
O
Chaillot
Bernard
B
Gerhardt
Roseline
R
Teulade
Jean-Claude
JC
Blache
Yves
Y
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000494:pharmacology*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D008288:Malaria / Q000517:prevention & control; D051379:Mice; D018512:Parasitemia / Q000517:prevention & control; D021261:Parasitic Sensitivity Tests; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000145:classification / Q000187:drug effects* / Q000254:growth & development; D013329:Structure-Activity Relationship
D000962:Antimalarials; D010618:Phenanthrolines; C025205:1,10-phenanthroline