Antimalarial activity of novel pyrrolizidinyl derivatives of 4-aminoquinoline.
Two pyrrolizidinylalkyl derivatives of 4-amino-7-chloroquinoline (MG2 and MG3) were prepared and tested in vitro against CQ-sensitive and CQ-resistant strains of Plasmodium falciparum and in vivo in a Plasmodium berghei mouse model of infection. Both compounds exhibited excellent activity in all tests and low toxicity against mammalian cells. Preliminary studies of the acute toxicity and of the metabolism of the most active compound MG3 indicate a promising profile as a new antimalarial drug candidate.
Sparatore
Anna
A
Istituto di Chimica Farmaceutica e Tossicologica Pietro Pratesi, University of Milan, Via Mangiagalli 25, 20133 Milan, Italy. anna.sparatore@unimi.it
Basilico
Nicoletta
N
Casagrande
Manolo
M
Parapini
Silvia
S
Taramelli
Donatella
D
Brun
Reto
R
Wittlin
Sergio
S
Sparatore
Fabio
F
D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001835:Body Weight; D002460:Cell Line; D002738:Chloroquine / Q000737:chemistry; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D008861:Microsomes / Q000187:drug effects; D008956:Models, Chemical; D010962:Plasmodium berghei / Q000378:metabolism; D010963:Plasmodium falciparum / Q000378:metabolism; D011758:Pyrroles / Q000737:chemistry*
D000634:Aminoquinolines; D000962:Antimalarials; D011758:Pyrroles; D002738:Chloroquine; C001920:4-aminoquinoline