title: New 4-aminobicyclo[2.2.2]octane derivatives and their activities against Plasmodium falciparum and Trypanosoma b. rhodesiense.
abstract: A series of new 2-substituted 4-dialkylaminobicyclo[2.2.2]octane derivatives was prepared and the compounds were investigated for their activity against causative organisms of tropical diseases. The tests were performed as microplate assays using the K1 strain of Plasmodium falciparum (resistant to chloroquine and pyrimethamine) and Trypanosoma brucei rhodesiense (STIB 900). The results were compared to the activities of former tested compounds of the bicyclo[2.2.2]octane series and to known drugs. Most of the 4-amino-6,7-diphenylbicyclo[2.2.2]octan-2-one thiosemicarbazones were compounds with attractive antimalarial potency (IC(50)=0.84-0.99microM, chloroquine: IC(50)=0.12microM). One of the bicyclo[2.2.2]octan-2-yl 4-tert-butylbenzenesulfonates showed the highest antitrypanosomal activity (IC(50)=0.68microM) of the so far prepared 4-amino-6,7-diarylbicyclo[2.2.2]octane derivatives, but is distinctly less active than suramin (IC(50)=0.0075microM).
authors.affiliation: Institute of Pharmaceutical Chemistry and Pharmaceutical Technology, Karl-Franzens-University, Universitätsplatz 1, A-8010, Graz, Austria. robert.weis@uni-graz.at
authors.forename: Werner
authors.initials: W
authors.lastname: Seebacher
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Robert
authors.initials: R
authors.lastname: Weis
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D020128:Inhibitory Concentration 50; D009795:Octanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D001643:Bridged Bicyclo Compounds; D009795:Octanes; D014344:Trypanocidal Agents