Location: Foodborne Toxin Detection and Prevention Research
Title: Antiprotozoal activity of palladium (II) salicylaldiminato thiosemicarbazone complexes on metronidazole resistant Trichomonas vaginalisAuthor
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CHELLAN, PRINESSA - University Of Cape Town |
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STRINGER, TAMERYN - University Of Cape Town |
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SHOKAR, AJIT - University Of The Pacific |
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AU, AARON - University Of The Pacific |
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Tam, Christina |
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Cheng, Luisa |
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SMITH, GREGORY - University Of Cape Town |
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LAND, KIRKWOOD - University Of The Pacific |
Submitted to: Inorganic Chemistry
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 1/23/2019 Publication Date: 1/25/2019 Citation: Chellan, P., Stringer, T., Shokar, A., Au, A., Tam, C.C., Cheng, L.W., Smith, G.S., Land, K.M. 2019. Antiprotozoal activity of palladium (II) salicylaldiminato thiosemicarbazone complexes on metronidazole resistant Trichomonas vaginalis. Inorganic Chemistry. (102):1-4. https://doi.org/10.1016/j.inoche.2019.01.033. DOI: https://doi.org/10.1016/j.inoche.2019.01.033 Interpretive Summary: Identifying new classes of compounds against infectious diseases is critical to finding new treatments, especially against drug resistant infections. Here, we tested a set of thiosemicarbazone compounds against a highly drug resistant isolate of the mucosal pathogen Trichomonas vaginalis. Two of the compounds in the library showed potency against the isolate. The two compounds also showed no detectable effects against a mammalian cell line. Since antibiotics often negatively impact the normal flora of a patient, we also screened the chemical library on several known normal flora bacteria and observed no effect on their growth at the highest concentration used in this study. Taken together, this study has identified several possible new leads for drug discovery against drug resistant Trichomonas vaginalis. Technical Abstract: Clinical cases of metronidazole resistant Trichomonas vaginalis infections have spurred interest in new drug discovery against this protozoal parasite. We have carried out a structure-activity analysis of 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 analyzed 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 analyzed 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. |