Design, synthesis, and biological activities of conformationally restricted analogs of primaquine with a 1,10-phenanthroline framework.
A series of primaquine analogs was prepared, according to a conformationally restricted conformation of primaquine. In vitro antiplasmodial activities were evaluated and showed that all compounds were active on different strains of Plasmodium falciparum. In particular compounds 5 and 15 possessing a methoxy group were more active than was primaquine. Furthermore, analog 5 displayed good in vitro gametocytocidal activity. In addition selectivity indexes were calculated in respect with cytotoxic activities on Vero cell lines.
Sall
Cheikh
C
Laboratoire de chimie organique et thérapeutique, EA 3660 Unité de Molécules d'Intérêt Biologique, Faculté de Pharmacie, 7 boulevard Jeanne d'Arc, BP 89700, 21079 Dijon, France.
Yapi
Ange-Désiré
AD
Desbois
Nicolas
N
Chevalley
Séverine
S
Chezal
Jean-Michel
JM
Tan
Kimny
K
Teulade
Jean-Claude
JC
Valentin
Alexis
A
Blache
Yves
Y
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002522:Chlorocebus aethiops; D002738:Chloroquine / Q000494:pharmacology; D015195:Drug Design; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008968:Molecular Conformation; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects; D011319:Primaquine / Q000737:chemistry; D014709:Vero Cells
D000962:Antimalarials; D010618:Phenanthrolines; D002738:Chloroquine; D011319:Primaquine; C025205:1,10-phenanthroline