Discovery of Potent and Selective Halogen-Substituted Imidazole-Thiosemicarbazides for Inhibition of Toxoplasma gondii Growth In Vitro via Structure-Based Design

Employing a simple synthetic protocol, a series of highly effective halogen-substituted imidazole-thiosemicarbazides with anti-Toxoplasma gondii effects against the RH tachyzoites, much better than sulfadiazine, were obtained (IC50s 10.30113.45 mu g/mL vs. 2721.45 mu g/mL). The most potent of them, 12, 13, and 15, blocked the in vitro proliferation of T. gondii more potently than trimethoprim (IC50 12.13 mu g/mL), as well. The results of lipophilicity studies collectively suggest that logP would be a rate-limiting factor for the anti-Toxoplasma activity of this class of compounds.