Dataset Information

Library of Selenocyanate and Diselenide Derivatives as In Vivo Antichagasic Compounds Targeting Trypanosoma cruzi Mitochondrion.

ABSTRACT: Chagas disease is usually caused by tropical infection with the insect-transmitted protozoan Trypanosoma cruzi. Currently, Chagas disease is a major public health concern worldwide due to globalization, and there are no treatments neither vaccines because of the long-term nature of the disease and its complex pathology. Current treatments are limited to two obsolete drugs, benznidazole and nifurtimox, which lead to serious drawbacks. Taking into account the urgent need for strict research efforts to find new therapies, here, we describe the in vitro and in vivo trypanocidal activity of a library of selected forty-eight selenocyanate and diselenide derivatives that exhibited leishmanicidal properties. The inclusion of selenium, an essential trace element, was due to the well-known extensive pharmacological activities for selenium compounds including parasitic diseases as T. cruzi. Here we present compound 8 as a potential compound that exhibits a better profile than benznidazole both in vitro and in vivo. It shows a fast-acting behaviour that could be attributed to its mode of action: it acts in a mitochondrion-dependent manner, causing cell death by bioenergetic collapse. This finding provides a step forward for the development of a new antichagasic agent.

SUBMITTER: Martin-Escolano R

PROVIDER: S-EPMC8147293 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Library of Selenocyanate and Diselenide Derivatives as In Vivo Antichagasic Compounds Targeting <i>Trypanosoma cruzi</i> Mitochondrion.

Martín-Escolano Rubén R Molina-Carreño Daniel D Plano Daniel D Espuelas Socorro S Rosales María J MJ Moreno Esther E Aydillo Carlos C Sanmartín Carmen C Sánchez-Moreno Manuel M Marín Clotilde C

Pharmaceuticals (Basel, Switzerland) 20210501 5

Chagas disease is usually caused by tropical infection with the insect-transmitted protozoan <i>Trypanosoma cruzi</i>. Currently, Chagas disease is a major public health concern worldwide due to globalization, and there are no treatments neither vaccines because of the long-term nature of the disease and its complex pathology. Current treatments are limited to two obsolete drugs, benznidazole and nifurtimox, which lead to serious drawbacks. Taking into account the urgent need for strict research ...[more]

PMID: 34062791

Similar Datasets

Project description:disease is one of the most neglected tropical diseases in the world, affecting nearly 15 million people, primarily in Latin America. Only two drugs are used for the treatment of this disease, nifurtimox and benznidazole. These drugs have limited efficacy and frequently induce adverse effects, limiting their usefulness. Consequently, new drugs must be found. In this study, we demonstrated the in vitro trypanocidal effects of a series of four gallic acid derivatives characterized by a gallate group linked to a triphenylphosphonium (TPP(+)) moiety (a delocalized cation) via a hydrocarbon chain of 8, 10, 11, or 12 atoms (TPP(+)-C8, TPP(+)-C10, TPP(+)-C11, and TPP(+)-C12, respectively). We analyzed parasite viability in isolated parasites (by MTT reduction and flow cytometry) and infected mammalian cells using T. cruzi Y strain trypomastigotes. Among the four derivatives, TPP(+)-C10 and TPP(+)-C12 were the most potent in both models, with EC50 values (in isolated parasites) of 1.0 ± 0.6 and 1.0 ± 0.7 μM, respectively, and were significantly more potent than nifurtimox (EC50 = 4.1 ± 0.6 μM). At 1 μM, TPP(+)-C10 and TPP(+)-C12 induced markers of cell death, such as phosphatidylserine exposure and propidium iodide permeabilization. In addition, at 1 μM, TPP(+)-C10 and TPP(+)-C12 significantly decreased the number of intracellular amastigotes (TPP(+)-C10: 24.3%, TPP(+)-C12: 19.0% of control measurements, as measured by DAPI staining) and the parasite's DNA load (C10: 10%, C12: 13% of control measurements, as measured by qPCR). Based on the previous mode of action described for these compounds in cancer cells, we explored their mitochondrial effects in isolated trypomastigotes. TPP(+)-C10 and TPP(+)-C12 were the most potent compounds, significantly altering mitochondrial membrane potential at 1 μM (measured by JC-1 fluorescence) and inducing mitochondrial transition pore opening at 5 μM. Taken together, these results indicate that the TPP(+)-C10 and TPP(+)-C12 derivatives of gallic acid are promising trypanocidal agents with mitochondrial activity.

Dataset Information

Library of Selenocyanate and Diselenide Derivatives as In Vivo Antichagasic Compounds Targeting Trypanosoma cruzi Mitochondrion.

Publications

Library of Selenocyanate and Diselenide Derivatives as In Vivo Antichagasic Compounds Targeting <i>Trypanosoma cruzi</i> Mitochondrion.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets