Abstract
In the present study, a family of 15 imidothio- and imidoselenocarbamates (1–15) analogs have been synthesized and screened for their in vitro antileishmanial potential against Leishmania infantum promastigotes. The six most active ones (2, 4, 7, 13, 14, and 15) were also tested in an axenic amastigote model. In order to establish their selectivity indexes (SI) the cytotoxic effect of each compound was also assayed against Jurkat and THP-1 cell lines. Compounds 2 and 4, both with a pyridine moiety, showed a moderate antileishmanial activity with an IC50 value of 4.68 ± 0.46 and 3.03 ± 0.24 μM, respectively, in the amastigote model. The activity was compared with that of standard drugs, edelfosine (IC50 = 0.82 ± 0.13 μM) and miltefosine (IC50 = 2.84 ± 0.10 μM). Related to selectivity, the SI of both compounds are similar to those of the standard drugs when compared against the THP-1 cell line. Moreover, compound 4 was able to reduce the number of amastigote-infected THP-1 cells to 40% of that observed in untreated controls after a 96-h period of treatment. These derivatives thus represent two new leads for further studies aimed at establishing their mechanism of action.
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Acknowledgments
The authors wish to express their gratitude to the University of Navarra Research Plan (Plan de Investigación de la Universidad de Navarra, PIUNA) and CAN Foundation for financial support for the project. The authors also acknowledge financial support from the Ministerio de Educación y Ciencia, Spain (grant SAF 2006-12713-CO2-O2; grant SAF 2009-13914-CO2-O2). We also thank Kilian Gutiérrez for his assistance in the cytotoxicity assays.
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In vitro activities of compounds against L. infantum promastigotes expressed as percentage of growth inhibition (DOC 58 kb)
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Moreno, D., Plano, D., Baquedano, Y. et al. Antileishmanial activity of imidothiocarbamates and imidoselenocarbamates. Parasitol Res 108, 233–239 (2011). https://doi.org/10.1007/s00436-010-2073-x
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DOI: https://doi.org/10.1007/s00436-010-2073-x