Last Updated: 05/10/2023
Pharmacological evaluation of gold compounds for the treatment of experimental malaria.
Objectives
*Original title in Portuguese: Avaliação farmacológica de compostos de ouro para o tratamento da malária experimental
This project will study the antimalarial profile of gold compounds conjugated with quinolines.
Gold compounds, such as auranofin, have antiparasitic potential in malaria by inhibiting the enzymatic activity of TrxRs, however, these are relatively weak antiparasitic agents and do not show efficacy in vivo. It is possible that the increased accumulation of gold compounds in Plasmodium cells increases the access of TrxR inhibitors to their biological target. One way to increase the accumulation of gold compounds in Plasmodium cells would be through conjugation with a molecule that has a high rate of accumulation in Plasmodium. Quinolines, such as Amodiaquine (AQ), accumulate in the digestive vacuole of Plasmodium with high efficiency (mechanism of “ion trapping” or ion sequestration). At the same time, the conjugation of AQ to gold would benefit AQ, since AQ has a biological target only in the asexual blood stage (heme detoxification), while auranofin has a biological target, the TrxRs, which is conserved through the entire evolutionary cycle of Plasmodium.
Jan 2021
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