Synthesis, antimalarial activity, and cellular toxicity of new arylpyrrolylaminoquinolines.
A set of nine new arylpyrrolyl derivatives of 7-chloro-4-aminoquinoline, characterized by different substituents on the phenyl ring or different distance between the pyrrolic nitrogen and the 4-aminoquinoline, has been synthesized and tested for their activity against D-10 (CQ-S) and W-2 (CQ-R) strains of Plasmodium falciparum. All compounds exhibited activity against the CQ-S strain in the low nM range, comparable to that of chloroquine. Some of them were also highly active against the CQ-R strain and not toxic against normal cells. The antimalarial activity of this new class of compounds seems to be related to the inhibition of heme detoxification process of parasites, as in the case of chloroquine.
Casagrande
Manolo
M
Dipartimento di Scienze Farmaceutiche Pietro Pratesi, Università degli Studi di Milano, Via Mangiagalli, 25, 20133 Milan, Italy.
Basilico
Nicoletta
N
Rusconi
Chiara
C
Taramelli
Donatella
D
Sparatore
Anna
A
D000634:Aminoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002460:Cell Line; D006420:Hemeproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects; D011758:Pyrroles / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000634:Aminoquinolines; D000962:Antimalarials; D006420:Hemeproteins; D011758:Pyrroles; C047186:7-chloro-4-aminoquinoline; C020753:hemozoin