New derivatives of 3-azabicyclo[3.2.2]nonanes and their antiprotozoal activities
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New derivatives of 3-azabicyclo[3.2.2]nonanes were prepared and characterized using FT-IR spectroscopy, HRMS, and NMR spectroscopy. The new compounds were investigated in vitro for their antiplasmodial activities against the sensitive NF54 strain and the multiresistant K1 strain of Plasmodium falciparum, and for their antitrypanosomal activity against Trypanosoma brucei rhodesiense. The N-methyl-6,9-diphenyl-N-[(pyridin-4-yl)methyl]-3-azabicyclo[3.2.2]nonan-1-amine possessed high antiplasmodial in vitro activity against both strains of P. falciparum (NF54: IC50 = 0.848 nm; K1: IC50 = 2 nm). The most promising ones were further investigated in a mouse model for their in vivo activity against Plasmodium berghei.
KeywordsAmines Antiplasmodial activity Antitrypanosomal activity Drug research Hybrids Structure–activity relationships
Compliance with ethical standards
In vivo efficacy studies in mice were conducted at the Swiss Tropical and Public Health Institute (Basel) according to the rules and regulations for the protection of animal rights (“Tierschutzverordnung”) of the Swiss “Bundesamt für Veterinärwesen”. They were approved by the veterinary office of Canton Basel-Stadt, Switzerland.
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