title: New derivatives of 7-chloroquinolin-4-amine with antiprotozoal activity.
abstract: Novel ω-aminoacyl and -alkyl derivatives of 7-chloroquinolin-4-amine were prepared and their structures confirmed by NMR spectroscopy. Their antiprotozoal activities were examined in vitro against the sensitive NF54 strain as well as against the multiresistant K1strain of Plasmodium falciparum and against Trypanosoma brucei rhodesiense (STIB 900). The results were compared with the activities of clinically used drugs. Their antitrypanosomal activities were only moderate whereas their antiplasmodial activities looked very promising. Some were equal or slightly more active than chloroquine against the sensitive strain. However, in comparison to chloroquine, the activity of the new compounds was decreased much less in the resistant strain. Several possessed activity against both strains in low nanomolar concentration.
authors.affiliation: Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Austria. Electronic address: johanna.faist@uni-graz.at.
authors.forename: Johanna
authors.initials: J
authors.lastname: Faist
authors.affiliation: Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Austria.
authors.forename: Clemens
authors.initials: C
authors.lastname: Hinteregger
authors.affiliation: Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Seebacher
authors.affiliation: Institute for Chemistry and Technology of Materials (ICTM), University of Technology Graz, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Saf
authors.affiliation: Swiss Tropical and Public Health Institute, and University of Basel, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Mäser
authors.affiliation: Swiss Tropical and Public Health Institute, and University of Basel, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.affiliation: Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Weis
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D051381:Rats; D013329:Structure-Activity Relationship; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects*
chemical_list: D000634:Aminoquinolines; D000981:Antiprotozoal Agents
keywords: Amines; Antiplasmodial activity; Heterocycles; NMR spectroscopy; Nucleophilic substitutions; Quinoline