Activity of Carbazole, Aminoguanidine and Diamine Anti-infectives against Toxoplasma gondii.

We report the observation that carbazole anti-infectives developed as antibacterial and antifungal drug leads have activity against the tachyzoite-stage growth of the Apicomplexan parasite Toxoplasma gondii with IC50 values as low as 2 μM. We show that a phenylthiazole aminoguanidine with antibacterial as well as antifungal activity inhibits growth with an IC50 value of 2.1 μM. We also tested a series of 18 analogs of the diamine SQ109, a tuberculosis drug candidate which likewise has both antibacterial and antifungal activity, finding activity as low as 2.3 μM. We tested all compounds for their activity in collapsing the ΔpH component of the promotive force, the results indicating that all compounds acted, at least in part, as protonophore uncouplers. Finally, we also investigated the correlation between the activity of all compounds against the yeast Saccharomyces cerevisiae and the bacterium Mycobacterium smegmatis, finding significant correlations between the collapse of the proton motive force and anti-fungal/antibacterial activity.