A series of trisubstituted 1,10-phenanthrolines was prepared. These compounds exhibited mild to high biological activities in vitro both toward chloroquino-resistant FcB1-Columbia and FcM29-Cameron strains and Nigerian chloroquino-sensitive strain of Plasmodium falciparum. Cytotoxicity of the most active compounds was estimated showing that one compound (10) exhibited a selective activity against malaria parasite (selectivity indexes of 52 and 144). Antiplasmodial activity of this derivative was optimized by N-10 alkylation and the phenanthrolinium salt (15) submitted to an in vivo study using mice infected by P. vinckei petteri showing an ED50 of 7.86 mg/kg/day.