title: New N-methylpiperazinyl derivatives of bicyclic antiprotozoal compounds.
abstract: The 4-methylpiperazinyl group was inserted as substituent at the bridgehead of bicyclic compounds or as terminal group of their aminoacyl and aminoalkyl side chains. The new compounds were tested in vitro for their activities against the multidrug-resistant K(1) strain of Plasmodium falciparum and Trypanosoma brucei rhodesiense (STIB 900). The results were compared to those of formerly prepared analogues and of drugs in use. A couple of bicyclo-octyl ω-(4-piperazin-1-yl)alkanoates showed high antitrypanosomal (IC(50)≤0.087μM) and antiplasmodial activity (IC(50)≤0.06μM). The most active ω-(4-methylpiperazin-1-yl)alkyl-2-azabicyclo-nonane possessed higher antiplasmodial activity (IC(50)≤0.023μM) and selectivity (S.I.=IC(50) (Cytotox.)/IC(50) (P. falciparum)=2188) than the antimalarial drug chloroquine (IC(50)=0.15μM, S.I.=1257).
authors.affiliation: Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl-Franzens University, Universitätsplatz 1, A-8010 Graz, Austria.
authors.forename: Johanna
authors.initials: J
authors.lastname: Faist
authors.forename: Werner
authors.initials: W
authors.lastname: Seebacher
authors.forename: Robert
authors.initials: R
authors.lastname: Saf
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.forename: Robert
authors.initials: R
authors.lastname: Weis
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects*; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects*
chemical_list: D000981:Antiprotozoal Agents; D001643:Bridged Bicyclo Compounds; D010879:Piperazines; D000077489:Piperazine