Short communication
Antiprotozoal activity of palladium(II) salicylaldiminato thiosemicarbazone complexes on metronidazole resistant Trichomonas vaginalis

https://doi.org/10.1016/j.inoche.2019.01.033Get rights and content

Highlights

  • Human trichomoniasis is caused by infection with the protozoal parasite Trichomonas vaginalis.

  • A clinical isolate that had failed three previous rounds of treatment with metronidazole was obtained from a patient.

  • Four thiosemicarbazones and their Pd(II) complexes were tested against this metronidazole resistant strain.

  • Three metal complexes showed promising inhibition and have been identified for further development.

Abstract

Clinical cases of metronidazole resistant Trichomonas vaginalis infections have spurred interest in drug discovery against this protozoal parasite. We have carried out structure-activity studies using mononuclear palladium(II) complexes containing salicylaldiminato thiosemicarbazones on a patient isolate of Trichomonas vaginalis highly resistant to the FDA-approved drug metronidazole. A small library of sixteen compounds were analysed on this resistant isolate. Interestingly, compared with our previous analysis of a metronidazole sensitive strain, susceptibility of this resistant isolate to four of the six most potent compounds was observed. Two compounds had similar IC50 values between the resistant strain and a previously analysed sensitive line. Palladium(II) salicylaldiminato thiosemicarbazone complexes may represent, with further development, a new drug discovery direction for treating clinical cases of metronidazole-resistant T. vaginalis. The most potent compound had an IC50 value of 15 μM on parasite growth and showed no effects on common normal flora bacteria and no morphological effects when tested on cultured mammalian cells.

Section snippets

Acknowledgements

We gratefully acknowledge our funders, the National Research Foundation (NRF) of South Africa, the University of Cape Town, and the Department of Biological Sciences and the Office of Grants and Sponsored Programs at the University of the Pacific. This work was also funded by the United States Department of Agriculture, Agricultural Research Service, National Program project NP108, CRIS 2030-42000-049-00D. We also thank our colleagues in the laboratory for insightful discussion and critical

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    Current Address: Stellenbosch University, Private Bag X1, Matieland, 7602, Western Cape, South Africa.

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