Table 1.
Available therapeutics for HAT.
Table 2.
DNDi target product profile for HAT.
Figure 1.
Reported anti-trypanosomal endoperoxides.
Figure 2.
Natural product analogues of merulin A.
Figure 3.
IC50 values against T. brucei brucei shown below each structure.
Table 3.
Comparison of computational pharmokinetic and pharmacodynamic properties of HAT therapeutics to merulin A analogues.
Figure 4.
Ester library biological data.
MW - Molecular weight; ADMET BBB – log of brain/blood partition coefficient; ADMET BBB Level – Ranking of the LogBB values into the following levels: 0 - Very high (value≥0.8), 1 – High (0.8>value≥0.0), 2 – Medium (0.0>value≥−0.8), 3 – Low (value<−0.8), 4 – Undefined; ADMET Hepatotoxicity Probability; ADMET PPB Level – plasma protein binding level: the lower the number the better; QED - quantitative estimate of drug-likeness: the bigger the number the more drug-like, weighted using QEDw,mo [17]. n.d. = not determined.
Figure 5.
Hydrophobicity vs. activity comparison within analog pairs.
Non-polar atoms are highlighted in blue, while the respective polar atoms are highlighted in red.
Figure 6.
Live trypanosome fluorescence imaging.
Diffuse cytoplasmic fluorescent signal of fluorophore conjugate 30, (a) indicating the uptake and accumulation of the compound into the cells. No fluorescence was detected in parasites treated with unlabeled compound 1 (b) or with free coumarin dye 31 (c).