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.
Istituto di Chimica Farmaceutica e Tossicologica Pietro Pratesi, University of Milan, Via Mangiagalli 25, 20133 Milan, Italy. anna.sparatore@unimi.it
Anna
A
Sparatore
Nicoletta
N
Basilico
Manolo
M
Casagrande
Silvia
S
Parapini
Donatella
D
Taramelli
Reto
R
Brun
Sergio
S
Wittlin
Fabio
F
Sparatore
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