Discovery of Potent and Selective Halogen-Substituted Imidazole-Thiosemicarbazides for Inhibition of <i>Toxoplasma gondii</i> Growth In Vitro via Structure-Based Design
Agata Paneth,
Lidia Węglińska,
Adrian Bekier,
Edyta Stefaniszyn,
Monika Wujec,
Nazar Trotsko,
Anna Hawrył,
Miroslaw Hawrył,
Katarzyna Dzitko
Affiliations
Agata Paneth
Department of Organic Chemistry, Medical University, Chodźki 4a, 20-093 Lublin, Poland
Lidia Węglińska
Department of Organic Chemistry, Medical University, Chodźki 4a, 20-093 Lublin, Poland
Adrian Bekier
Department of Immunoparasitology, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland
Edyta Stefaniszyn
Department of Organic Chemistry, Medical University, Chodźki 4a, 20-093 Lublin, Poland
Monika Wujec
Department of Organic Chemistry, Medical University, Chodźki 4a, 20-093 Lublin, Poland
Nazar Trotsko
Department of Organic Chemistry, Medical University, Chodźki 4a, 20-093 Lublin, Poland
Anna Hawrył
Department of Inorganic Chemistry, Medical University, Chodźki 4a, 20-093 Lublin, Poland
Miroslaw Hawrył
Department of Inorganic Chemistry, Medical University, Chodźki 4a, 20-093 Lublin, Poland
Katarzyna Dzitko
Department of Immunoparasitology, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland
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.
