title: Synthesis, antimalarial activity, and cellular toxicity of new arylpyrrolylaminoquinolines.
abstract: 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.
authors.affiliation: Dipartimento di Scienze Farmaceutiche Pietro Pratesi, Università degli Studi di Milano, Via Mangiagalli, 25, 20133 Milan, Italy.
authors.forename: Manolo
authors.initials: M
authors.lastname: Casagrande
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Basilico
authors.forename: Chiara
authors.initials: C
authors.lastname: Rusconi
authors.forename: Donatella
authors.initials: D
authors.lastname: Taramelli
authors.forename: Anna
authors.initials: A
authors.lastname: Sparatore
mesh_terms: 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
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D006420:Hemeproteins; D011758:Pyrroles; C047186:7-chloro-4-aminoquinoline; C020753:hemozoin