Synthesis of 3-azabicyclo[3.2.2]nonanes and their antiprotozoal activities.
Several bicyclic compounds, 3-azabicyclo[3.2.2]nonanes, have been prepared. The new compounds were tested for their activities against one strain of the causative organism of Malaria tropica, Plasmodium falciparum K1, which is resistant against chloroquine and pyrimethamine. In addition, their cytotoxicity and their activity against the pathogen of the East African form of sleeping sickness, Trypanosoma brucei rhodesiense, were investigated. Structure-activity relationships are discussed considering data of readily prepared compounds. For the first time, a distinct in vivo activity was observed against Plasmodium berghei in a mouse model. The active compound was further investigated.
Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl-Franzens-University, Schubertstrasse 1, Graz A-8010, Austria. Electronic address: we.seebacher@uni-graz.at.
Werner
W
Seebacher
Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl-Franzens-University, Schubertstrasse 1, Graz A-8010, Austria.
Volker
V
Wolkinger
Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl-Franzens-University, Schubertstrasse 1, Graz A-8010, Austria.
Johanna
J
Faist
Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel CH-4002, Switzerland; University of Basel, Petersplatz 1, Basel CH-4003, Switzerland.
Marcel
M
Kaiser
Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel CH-4002, Switzerland; University of Basel, Petersplatz 1, Basel CH-4003, Switzerland.
Reto
R
Brun
Institute for Chemistry and Technology of Materials (ICTM), Graz University of Technology, Stremayrgasse 9, Graz A-8010, Austria.
Robert
R
Saf
Institute of Pharmaceutical Sciences, Pharmacognosie, Karl-Franzens-University, Universitätsplatz 4, Graz A-8010, Austria.
Franz
F
Bucar
Institute of Pharmaceutical Sciences, Pharmacognosie, Karl-Franzens-University, Universitätsplatz 4, Graz A-8010, Austria.
Barbara
B
Gröblacher
Institute of Pharmaceutical Sciences, Pharmacognosie, Karl-Franzens-University, Universitätsplatz 4, Graz A-8010, Austria.
Adelheid
A
Brantner
Departamento de Farmacia y Tecnología Farmacéutica, University of Valencia, Valencia E-46000, Spain.
Virginia
V
Merino
School of Pharmaceutical Sciences, Pharmaceutical Biochemistry, University of Geneva, Quai Ernest-Ansermet 30, Geneva CH-1211, Switzerland.
Yogeshvar
Y
Kalia
School of Pharmaceutical Sciences, Pharmaceutical Biochemistry, University of Geneva, Quai Ernest-Ansermet 30, Geneva CH-1211, Switzerland.
Leonardo
L
Scapozza
School of Pharmaceutical Sciences, Pharmaceutical Biochemistry, University of Geneva, Quai Ernest-Ansermet 30, Geneva CH-1211, Switzerland.
Remo
R
Perozzo
Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl-Franzens-University, Schubertstrasse 1, Graz A-8010, Austria.
Robert
R
Weis
D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*; D051381:Rats; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D016833:Trypanosoma brucei rhodesiense / Q000166:cytology / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy*
D000981:Antiprotozoal Agents; D053961:Azabicyclo Compounds
3-Azabicyclo[3.2.2]nonanes; Antiplasmodial activity; Antitrypanosomal activity