Table 2.

Sensitivities of five P. falciparum strains to different falcipain-2 inhibitors

CompoundaIC50(nM) based on parasite development (metabolism) assayb
D6Dd2HB3ItGW2
Mu-Phe-Hph-CH2F0.90 (8.55)0.78 (4.87)0.66 (3.38)0.51 (9.18)0.81 (8.36)
Mu-Leu-HphVSPh1.51 (26.6)0.66 (13.0)1.60 (15.5)1.03 (29.2)1.20 (28.6)
N-Me-pipu-Leu-HphVSPh0.58 (9.93)0.40 (2.57)0.44 (2.87)0.60 (10.5)0.45 (5.21)
N-Me-pipu-Leu-HphVS-2Np0.22 (4.72)0.32 (4.36)0.19 (1.55)0.18 (2.02)0.20 (2.74)
Chloroquine1.74 (7.89)26.0 (158)1.40 (16.0)38.1 (153)17.7 (123)
  • a Mu-Phe-Hph-CH2F, morpholine urea-phenylalanine-homophenylalanine-fluoromethyl ketone; Mu-Leu-HphVSPh, morpholine urea-leucine-homophenylalanine-phenyl vinyl sulfone; N-Me-pipu-Leu-HphVSPh, N-methyl piperazine urea-leucine-homophenylalanine-phenyl vinyl sulfone;N-Me-pipu-Leu-HphVS-2Np, N-methyl piperazine urea-leucine-homophenylalanine-naphthalene vinyl sulfone.

  • b IC50s, determined from dose response curves, are shown for assays of parasite development (based on parasite counts) and metabolism (based on [3H]hypoxanthine uptake) performed as described in the text.