Available therapeutics for HAT.

<p>Available therapeutics for HAT.</p

DNDi target product profile for HAT.

*<p>It is expected that donor agencies will pay this, not patients. Considering that some 20,000–50,000 patients per year might require treatment, this is still realistic.</p

Reported anti-trypanosomal endoperoxides.

<p>Reported anti-trypanosomal endoperoxides.</p

Initial SAR analog library.

<p>IC₅₀ values against <i>T. brucei</i> brucei shown below each structure.</p

Live trypanosome fluorescence imaging.

<p>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 <b>1</b> (b) or with free coumarin dye <b>31</b> (c).</p

Comparison of computational pharmokinetic and pharmacodynamic properties of HAT therapeutics to merulin A analogues.

<p>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 QED_w,mo. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046172#pone.0046172-Bickerton1" target="_blank">[17]</a>.</p

Ester library biological data.

<p>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 QED_w,mo<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046172#pone.0046172-Bickerton1" target="_blank">[17]</a>. <i>n.d.</i> = not determined.</p

Natural product analogues of merulin A.

<p>Natural product analogues of merulin A.</p

Hydrophobicity <i>vs.</i> activity comparison within analog pairs.

<p>Non-polar atoms are highlighted in blue, while the respective polar atoms are highlighted in red.</p