title: Antiprotozoal activity of bicyclic diamines with a N-methylpiperazinyl group at the bridgehead atom.
abstract: ω-Aminoacyl and -alkyl derivatives of 4-(4-methylpiperazin-1-yl)bicyclo[2.2.2]octan-2-amines and of 5-(4-methylpiperazin-1-yl)-2-azabicyclo[3.2.2]nonanes were prepared and their activities were examined in vitro against the multiresistant K1 strain of Plasmodium falciparum and against Trypanosoma brucei rhodesiense (STIB 900). Some of the newly synthesized compounds showed very promising antiprotozoal activity and selectivity. A few of the alkylamino-2-azabicyclo[3.2.2]nonanes exhibited high antiplasmodial activity, whereas a single bicyclo[2.2.2]octane derivative was the most potent antitrypanosomal compound. The results of the newly synthesized compounds were compared with the activities of already synthesized compounds and of drugs in use. Structure-activity relationships were discussed.
authors.affiliation: Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Stremayrgasse 16, A-8010 Graz, Austria. johanna.faist@uni-graz.at
authors.forename: Johanna
authors.initials: J
authors.lastname: Faist
authors.forename: Werner
authors.initials: W
authors.lastname: Seebacher
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Robert
authors.initials: R
authors.lastname: Saf
authors.forename: Robert
authors.initials: R
authors.lastname: Weis
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D021261:Parasitic Sensitivity Tests; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects
chemical_list: D000981:Antiprotozoal Agents; D001643:Bridged Bicyclo Compounds; D010879:Piperazines; D000077489:Piperazine
keywords: 4-(4-Methylpiperazin-1-yl)bicyclo[2.2.2]octanes; 5-(4-Methylpiperazin-1-yl)-2-azabicyclo[3.2.2]nonanes; Plasmodium falciparum; Trypanosoma brucei rhodesiense