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

Abstract

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 10.30—113.45 µg/mL vs. ~2721.45 µg/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 µg/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.

Keywords

• thiosemicarbazides
• anti-<i>Toxoplasma gondii</i> activity
• cytotoxicity
• selectivity ratio
• structure-activity relationship (SAR) analysis