TABLE 2

List of drugs assayed, IC50s, IPP rescue, and impact on the apicoplasta

NameNo. of exptsIC50 (mean ± SD) (μM)Growth rescue by IPP supplementationLoss of apicoplastb:Known/putative target(s)cReference(s)
Cycle 1, 48 hCycle 2, 120 hGenomeProtein importStructure
Chloroquine20.032 ± 0.0020.018 ± 0.002NANANAHeme polymerization, food vacuole43
Atovaquone20.0008 ± 0.00030.0007 ± 0.0001NANANACytochrome b, mitochondria46
Ciprofloxacin333.7 ± 3.69.1 ± 3.2++++DNA gyrase, prokaryotic DNA synthesis, apicoplast103, 104
Rifampin32.3 ± 0.31.06 ± 0.3NANANAPlastid RNA polymerase β-subunit (rpoB), apicoplast (predicted)125
Chloramphenicol2847.6 ± 58.431.4 ± 4.3++++Prokaryotic protein synthesis, apicoplast37, 94
Doxycycline512.7 ± 1.21.9 ± 0.9++++Prokaryotic protein synthesis, plastid 16S rRNA (rrnS), apicoplast126
Tetracycline364.4 ± 2.82.4 ± 1.7++++70S ribosomes, prokaryotic protein synthesis, apicoplast126
Clindamycin3262.5 ± 44.20.04 ± 0.01++++Prokaryotic protein synthesis, apicoplast121
Azithromycin39.8 ± 1.00.06 ± 0.02++++Prokaryotic protein synthesis, apicoplast18, 33, 34
Erythromycin4130.4 ± 5.65.8 ± 0.7++++Prokaryotic protein synthesis, apicoplast34, 91, 127
Clarithromycin233.0 ± 1.16.4 ± 0.3++++Prokaryotic protein synthesis, apicoplast128
Fusidic acid257.6 ± 8.932.9 ± 3.6NANANAProkaryotic protein synthesis, apicoplast (predicted)59, 60
Toltrazuril5318.8 ± 40.7108.2 ± 31.4NANANAProkaryotic protein synthesis, D1-water-splitter protein of photosystem II (psbA), apicoplast (predicted)71
Mupirocin4313.4 ± 44.40.14 ± 0.06++++Isoleucyl-tRNA synthetase (IleRS) inhibitor109, 110
Borrelidin20.0018 ± 0.00090.0017 ± 0.0008NANANABacterial and eukaryotic threonyl-tRNA synthetase (ThrRS) enzymes111114
Actinonin34.9 ± 1.11.9 ± 0.7++++Prokaryotic protein synthesis, PDF64, 69, 70
Fosmidomycin31.0 ± 0.20.8 ± 0.2+DOXP reductoisomerase and MEP cytidyltransferase (IspD) pathway, apicoplast19, 47, 48, 50, 129
FR90009821.0 ± 0.10.5 ± 0.1+DOXP reductoisomerase and MEP cytidyltransferase (IspD) pathway, apicoplast19, 39
Triclosan41.3 ± 0.30.4 ± 0.1NANANAEnoyl-ACP reductase/Fab I, type II fatty acid synthesis, apicoplast (predicted)75
Cerulenin313.4 ± 1.713.9 ± 0.2NANANAFab B/F, type II fatty acid synthesis, apicoplast (predicted)76, 77
Hexachlorophene210.9 ± 3.34.3 ± 1.5NANANAFabG inhibitor, inhibit liver stage parasite development in vitro, apicoplast (predicted)78, 79
Succinylacetone3>1,600>1,600NANANAAminolevulinic acid dehydratase, heme synthesis, apicoplast (predicted)32
Brefeldin A32.3 ± 0.51.3 ± 0.3NANANAGolgi export81, 84, 130, 131
  • a Each drug concentration was assayed in triplicate.

  • b NA, not applicable.

  • c PDF, peptide deformylase; DOXP, 1-deoxy-d-xylulose 5-phosphate; MEP, methylerythritol phosphate; ACP, acyl carrier protein.