4-Aminoquinoline-based compounds as antileishmanial agents that inhibit the energy metabolism of Leishmania.

08:00 EDT 5th July 2019 | BioPortfolio

Summary of "4-Aminoquinoline-based compounds as antileishmanial agents that inhibit the energy metabolism of Leishmania."

Among neglected tropical diseases, leishmaniasis is one of the most relevant with an estimated 30,000 deaths annually. Existing therapies have serious drawbacks in safety, drug resistance, field-adapted application and cost; therefore, new safer and shorter treatments are needed for this disease. Here we report on the synthesis of novel 4-amino-7-chloroquinoline-based compounds with leishmanicidal activity, together with deeper insight into the mechanism of action of our previously published hit compound 1. New derivatives showed comparable activity to 1 against both promastigote and intracellular amastigote forms of Leishmania infantum, with IC < 1 μM. Furthermore, we have determined that compound 1 induced a decrease of intracellular ATP levels, as well as a mitochondrial depolarization, together with an alteration of plasma membrane permeability and a significant ROS production. The inhibition of the energy metabolism of Leishmania plays an important role in the leishmanicidal mechanism of this compound. In all, these results support the consideration of compound 1 for the future development of new leishmanicidal drugs.


Journal Details

This article was published in the following journal.

Name: European journal of medicinal chemistry
ISSN: 1768-3254
Pages: 28-40


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