Increasing the activity of copper(II) complexes against Leishmania through lipophilicity and pro-oxidant ability
Andressa dos Santos Portas1, Danilo Ciccone Miguel, Jenicer K U Yokoyama-Yasunaka
1Instituto de Química, Universidade de São Paulo, Av Lineu Prestes 748, 05508-000 São Paulo, SP, Brazil.
Abstract:
Copper complexes with fluorinated β-diketones were synthesized and characterized in terms of lipophilicity and peroxide-assisted oxidation of dihydrorhodamine as an indicator of redox activity. The biological activity of the complexes was tested against promastigotes of Leishmania amazonensis. Inhibition of trypanosomatid-specific trypanothione reductase was also tested. It was found that the highly lipophilic and redox-active bis(trifluoroacetylacetonate) derivative had increased toxicity towards promastigotes. These results indicate that it is possible to modulate the activity of metallodrugs based on redox-active metals through the appropriate choice of lipophilic chelators in order to design new antileishmanials. Further work will be necessary to improve selectivity of these compounds against the parasite.
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