Sulfonamide and urea derivatives of quinacrine with varying methylene spacer lengths were synthesised and tested for inhibition of trypanothione reductase (TryR) and for activity in vitro against strains of the parasitic protozoa Trypanosoma, Leishmania, and Plasmodium. These derivatives are superior inhibitors of TryR relative to quinacrine with the best compound being 40 times more potent. Urea derivatives generally displayed good in vitro activity against all parasites.