Here we reported our investigation, as part of our
drug repositioning effort, on anti-Toxoplasma properties of newly synthesized
quinoline compounds. A collection of
4-aminoquinoline and 4-piperazinylquinoline analogs have recently been synthesized for use in
cancer chemotherapy. Some analogs were able to outperform
chloroquine, a
quinoline derivative
drug which is commonly used in the treatment of
malaria and other
parasitic infections. Herein 58 compounds containing one or two
quinoline rings were examined for their effectiveness as potential anti-Toxoplasma compounds. Of these 58 compounds, 32 were efficient at inhibiting Toxoplasma growth (IC50<100 μM). Five compounds with single and simple
quinoline rings exhibited similar cLogP values of ∼2 and IC50 values between 5 and 6 μM, with one exception of
8-hydroxyquinoline whose IC50 value was 213 nM. The addition of one
hydroxyl group at position 8 caused a 40-fold increase in the inhibitory effect of
quinoline. A significant improvement in anti-Toxoplasma effect among
quinoline derivatives was detected in B11, B12, B23, and B24, whose structures carry two
quinoline rings, and their resultant cLogP values are ⩾7. Among these compounds, B23 was the most effective compound with IC50 value of 425±35 nM, and TI value of 4.9. It was also noted that compounds with at least one
quinoline ring, displaying anti-Toxoplasma effects were capable of causing the disappearance of the apicoplast, a plastid-like organelle. When treated with
quinoline,
8-hydroxyquinoline or B23, 40-45% of the parasites lost their apicoplasts. Our findings recapitulate the properties of
quinoline derivatives in diminishing apicoplast. This could aid further investigations of anti-parasitic treatments specific to Apicomplexan. More importantly, B12 and B23 which harbor superior anti-
cancer properties than
chloroquine, have effective anti-Toxoplasma activity. These compounds therefore have significant potential for future development of chemotherapeutic agents for patients suffering from breast
cancers and
parasitic infection.