Table 2.
Most active compounds tested by St Jude’s Children’s Research Hospital
Compound | Class (therapeutic area) | EC 50 3D7 (μM) | EC 50 K1 (μM) |
---|---|---|---|
Methylene blue |
Nitric oxide/guanylate cyclase inhibitor (various) |
<0.0003 (NA) |
<0.0003 (NA) |
Dactinomycin |
Nucleoside reverse transcriptase inhibitor (oncology) |
0.0009 (0, 0.13) |
0.001 (0.0003, 0.006) |
Sulfamerazine |
Dihydrofolate synthetase inhibitor (anti-infective) |
0.01 (0.01, 0.01) |
0.01 (0.01, 0.01) |
Methotrexate |
Dihydrofolate reductase inhibitor (oncology) |
0.01 (0.009, 0.01) |
0.02 (0.01, 0.02) |
Bortezomib |
Proteasome inhibitor (oncology) |
0.02 (0.01, 0.04) |
0.08 (0.07, 0.09) |
Thiothixene |
Post-synaptic receptor agonista (anti-psychotic) |
0.04 (0, 233.71) |
0.02 (0.01, 0.05) |
Dequalinium |
Anti-septic |
0.06 (0.002, 1.53) |
0.06 (0.03, 0.12) |
Doxorubicin |
Topoisomerase II inhibitor, DNA intercalating agent (oncology) |
0.21 (0.16, 0.27) |
0.20 (0.14, 0.30) |
Pentamidine |
Inhibition of DNA, RNA, phospholipid and protein synthesisb (anti-infective) |
0.22 (0.18, 0.27) |
0.05 (0.04, 0.06) |
Bosutinib |
Tyrosine kinase inhibitor (oncology) |
0.22 (0.016, 3.11) |
0.65 (0.36, 1.19) |
Aminopterin |
Dihydrofolate reductase inhibitor (oncology) |
0.32 (0.30, 0.33) |
1.25 (1.11, 1.41) |
Midostaurin |
Multi-kinase inhibitor (oncology) |
0.35 (0.17, 0.71) |
0.15 (0.13, 0.17) |
Lestaurtinib |
FMS-like tyrosine kinase 3 inhibitor (oncology) |
0.49 (0.28, 0.84) |
0.34 (0.29, 0.41) |
Demecarium |
Cholinesterase inhibitor (ophthalmology) |
0.51 (0.45, 0.57) |
0.30 (0.26, 0.36) |
Cyproterone |
Steroidal anti-androgen (oncology) |
0.56 (0.54, 0.58) |
0.89 (0, 1501.50) |
Lapatinib |
Tyrosine kinase inhibitor (oncology) |
0.56 (0.39, 0.80) |
>7.37 (NA) |
Pimozide |
Dopamine receptor blocker (anti-psychotic) |
0.70 (0.44, 1.11) |
>12.76 (NA) |
Pravastatin |
HMG-CoA reductase inhibitor (anti-cholesterol) |
0.75 (0.51, 1.09) |
0.12 (0.10, 0.15) |
Dipyrone |
NSAIDb (pain) |
0.84 (0.71, 0.98) |
0.50 (0.21, 1.16) |
Mitomycin |
Inhibition of DNA synthesis (oncology) |
0.97 (0.81, 1.17) |
0.51 (0.45, 0.57) |
Propafenone |
Sodium channel modulator (cardiology) |
1.22 (0.58, 2.55) |
0.33 (0.31, 0.34) |
Cyclosporin A |
Immune suppressant (oncology) |
1.23 (1.06, 1.44) |
0.87 (0.62, 1.23) |
Vorinostat |
Histone deacetylase inhibitor (oncology) |
1.47 (1.17, 1.84) |
0.84 (0.76, 0.93) |
Sorafenib | Multi-kinase inhibitor (oncology) | 2.71 (2.4, 3.1) | 0.88 (0.7, 1.1) |
NA, not available. EC50 values are shown as mean (95% CI). Compounds with an EC50 < 1 μM against either P. falciparum strain are shown. Relevant results from all compound sets tested at SJCRH are shown. Where compounds were duplicated across the consolidated test set, the results with the most potent in vitro activity are shown. Known anti-malarial drugs have been excluded.
aAgonist of dopaminergic-receptors, serotonergic-receptors, histaminergic-receptors, alpha1/alpha2-receptors, and muscarinic (cholinergic) M1/M2-receptors.
bMechanism unknown.
SYBR®I fluorescence assay for activity against P. falciparum strains 3D7 and K1.