Abstract
Toxoplasmosis is a common parasitic disease caused by Toxoplasma gondii. Limitations of available treatments motivate the search for better therapies for toxoplasmosis. In this study, we synthesized a series of new imidazole derivatives: bis-imidazoles (compounds 1–8), phenyl-substituted 1H-imidazoles (compounds 9–19), and thiopene-imidazoles (compounds 20–26). All these compounds were assessed for in vitro potential to restrict the growth of T. gondii. To explore the structure–activity relationships, molecular analyses and bioactivity prediction studies were performed using a standard molecular model. The in vitro results, in combination with the predictive model, revealed that the imidazole derivatives have excellent selectivity activity against T. gondii versus the host cells. Of the 26 compounds screened, five imidazole derivatives (compounds 10, 11, 18, 20, and 21) shared a specific structural moiety and exhibited significantly high selectivity (> 1176 to > 27,666) towards the parasite versus the host cells. These imidazole derivatives are potential candidates for further studies. We show evidence that supports the antiparasitic action of the imidazole derivatives. The findings are promising in that they reinforce the prospects of imidazole derivatives as alternative and effective antiparasitic therapy as well as providing evidence for a probable biological mechanism.
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Acknowledgments
The authors would like to thank the Department for Management of Science and Technology Development, Faculty of Applied Science, Ton Duc Thang University, Ho Chi Minh City. The JSPS Fellowship to OS Adeyemi is also acknowledged. Also, AO Eseola appreciates the Alexander von Humboldt Foundation support through the Georg Forster postdoctoral scholarship and the Redeemer’s University for fellowship leave. Additionally, the financial support by the Deutsche Forschungsgemeinschaft (DFG) is appreciated (PL 155/11, PL 155/12, and PL155/13). For editorial assistance, our appreciation goes to Ed and Rhoda Perozzi and Carey Johnson of the Chemistry Department, University of Kansas, USA.
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Section Editor: Xing-Quan Zhu
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CCDC 850686, 1897702, and 1897701 contain the supplementary crystallographic data for compounds C-7, C-10, and C-25, respectively. These data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44 01223 336033; e-mail: deposit@ccdc.cam.ac.uk).
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Adeyemi, O.S., Eseola, A.O., Plass, W. et al. Imidazole derivatives as antiparasitic agents and use of molecular modeling to investigate the structure–activity relationship. Parasitol Res 119, 1925–1941 (2020). https://doi.org/10.1007/s00436-020-06668-6
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DOI: https://doi.org/10.1007/s00436-020-06668-6