Fig. 6: Cellular activities of triple-site ProRS inhibitors.

a In vitro activity of pyrazinamide-halofuginone hybrids and Boc-protected precursors against wild-type ABS P. falciparum Dd2-2D4. b In vitro activity of pyrazinamide-halofuginone hybrids against halofuginone-induced (HFG-Induced, squares and dashed lines) and HFGR-I (triangles and dotted lines) ABS P. falciparum. c In vitro activity of NCP26 and MAT436 against liver stage P. berghei (solid circles) and HuH7 liver cells (open circles). In a–c, inhibitors are color coded: 35 (dark blue), 36 (light gray), 37 (dark gray), 38 (blue), 39 (red), MAT436 (gray), iso-MAT436 (light blue), and NCP26 (orange). ABS growth assay data in a and b are expressed as mean ± s.d. (n = 3 biological replicates) and are representative of at least three independent experiments, except for compound 39 which is only representative of two independent experiments for Dd2-2D4 in a. Liver stage and HuH7 data in c are expressed as mean ± s.d. (n = 3 biological replicates) and are representative of at least three independent experiments.