New Amides Containing Selenium as Potent Leishmanicidal Agents Targeting Trypanothione Reductase

2020/10/07 by Mikel Etxebeste-Mitxeltorena, Daniel Plano, Socorro Espuelas +7
Medicine · Chemistry · #Research on Leishmaniasis Studies #Trypanosoma species research and implications #Synthesis and Biological Evaluation

paper · doi:10.1128/aac.00524-20

Abstract

values of 0.52, 1.19, and 0.50 μM, respectively, and a high selectivity index (SI) when tested against THP-1 monocytic cells (SI = >1,442, >672, and >1,100, respectively). These derivatives showed an efficacy similar to that of the reference drugs but much better SI values. They also showed interesting activity values against infected macrophages. Trypanothione reductase (TryR) activity and intracellular thiol level measurement assays were performed for the three best compounds in an attempt to elucidate their mechanism of action. Despite that the new analogs exhibited comparable or better inhibitory activities than the reference TryR inhibitors, more studies are necessary to confirm this result. In summary, our findings suggest that the three compounds described here could constitute leading leishmanicidal drug candidates.

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