The imidazo[2,1-a]isoindole system. A new skeletal basis for antiplasmodial compounds.
The in vitro antiplasmodial activity of some dihydrostilbenamides, phtalazinones, imidazo[2,1-a]isoindole and pyrimido[2,1-a]isoindole derivatives related to the natural dihydrostilbenoid isonotholaenic acid is reported. The evaluation was performed on cultures of F32 strain of Plasmodium falciparum and potent representative compounds were also evaluated in the ferriprotoporphyrin IX biomineralization inhibition test (FBIT). Compounds having the imidazo[2,1-a]isoindole skeleton were the most active and one compound of this group resulted to be as potent as chloroquine, but acting through a mechanism different that of the inhibition of heme biomineralization.
del Olmo
Esther
E
Departamento de Química Farmacéutica, Facultad de Farmacia, 37007-Salamanca, Spain. olmo@usal.es
Armas
Marlon García
MG
Ybarra
MaInés
M
López
Josè Luis
JL
Oporto
Patricia
P
Giménez
Alberto
A
Deharo
Eric
E
San Feliciano
Arturo
A
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000962:Antimalarials; D007093:Imidazoles; D007211:Indoles; D002738:Chloroquine