Inhibitors of retrograde trafficking active against ricin and Shiga toxins also protect cells from several viruses, Leishmania and Chlamydiales.

Medical countermeasures to treat biothreat agent infections require broad-spectrum therapeutics that do not induce agent resistance. A cell-based high-throughput screen (HTS) against ricin toxin combined with hit optimization allowed selection of a family of compounds that meet these requirements. The hit compound Retro-2 and its derivatives have been demonstrated to be safe in vivo in mice even at high doses.

In vitro and in vivo antileishmanial properties of a 2-n-propylquinoline hydroxypropyl β-cyclodextrin formulation and pharmacokinetics via intravenous route.

2-n-propylquinoline (2-n-PQ) had shown interesting in vivo antileishmanial activities after administration by oral route on leishmaniasis animal models. However, the lipophilic properties of this compound avoid its use by intravenous route, this route being indicated in cases of severe visceral leishmaniasis with vomiting. Thus, a 2-n-propylquinoline hydroxypropyl beta-cyclodextrin (2-n-PQ-HPC) formulation was set up in this aim.

Selection of the most promising 2-substituted quinoline as antileishmanial candidate for clinical trials.

The antileishmanial evaluation of more than one hundred 2-substituted quinolines led us to identify three compounds for further studies: compound 1 (2-n-propylquinoline), compound 2 (2-(2methoxyethenyl)quinoline) and compound 3 (2-(2-hydroxyprop-2-enyl)quinoline). The final selection of a potential drug candidate was mainly based on chemical stability and acute oral toxicity as discriminating criteria. The most stable compound in various conditions was 2-n-propylquinoline (compound 1).