Synthesis of new esters and oximes with 4-aminobicyclo[2.2.2]octane structure and evaluation of their antitrypanosomal and antiplasmodial activities.
New 4-amino-6,7-diphenylbicyclo[2.2.2]octane derivatives, esters of bicyclo[2.2.2]octan-2-ols and O-methyl oximes of bicyclo[2.2.2]octan-2-ones were synthesised. Their activities against Trypanosoma brucei rhodesiense (STIB 900) and their activity against the K1 strain of Plasmodium falciparum (resistant to chloroquine and pyrimethamine) were determined by use of microplate assays. The cytotoxicity was assessed using L6 cells. The antiprotozoal activities of the new compounds are compared with those of former prepared derivatives and drugs in use. Structure-activity relationships are discussed.
Seebacher
W
W
Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl-Franzens-University, Universitätsplatz 1, A-8010 Graz, Austria. we.seebacher@uni-graz.at
Schlapper
C
C
Brun
R
R
Kaiser
M
M
Saf
R
R
Weis
R
R
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry* / Q000494:pharmacology*; D004952:Esters / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D010091:Oximes / Q000138:chemical synthesis*; D010963:Plasmodium falciparum / Q000187:drug effects; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects
C507161:4-aminobicyclo(2.2.2)octane; D000962:Antimalarials; D001643:Bridged Bicyclo Compounds; D004952:Esters; D010091:Oximes; D014344:Trypanocidal Agents