Withanolides from Withania aristata as Antikinetoplastid Agents through Induction of Programmed Cell Death

López-Arencibia, Atteneri; Nicolás-Hernández, Desirée San; Bethencourt-Estrella, Carlos J.; Sifaoui, Inés; Reyes-Batllé, María; Rodríguez-Expósito, Rubén L.; Rizo-Liendo, Aitor; Lorenzo‐Morales, Jacob; Bazzocchi, Isabel L.; Jiménez, Ignacio A.

doi:10.3390/pathogens8040172

Cited by 16 publications

(7 citation statements)

References 26 publications

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“…Apoptosis in African trypanosomes has also been reported as a consequence of the treatment with methanol, butanol, and dichloromethane extracts of the leaves and roots from Zanthoxylum zanthoxyloides and for withanolides derived from Withania aristata . In this case, withanolides showed antikinetoplastid activity, and their mechanism of action was the induction of programmed cell death …”

Section: Resultsmentioning

confidence: 95%

Linearolactone and Kaempferol Disrupt the Actin Cytoskeleton in Entamoeba histolytica: Inhibition of Amoebic Liver Abscess Development

et al. 2020

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Linearolactone (1) and kaempferol (2) have amebicidal activity in in vitro studies. The type of cell death induced by 1 and 2 and their effects on the virulence of E. histolytica were analyzed by transmission and confocal electron microscopy, reactive oxygen species (ROS) production, and apoptosis, detected by flow cytometry with dichlorofluorescein 2′,7′-diacetate and annexin-V binding, respectively, and confirmed by TUNEL. The interaction of 1 and 2 with actin was analyzed by docking, and the in vivo amoebicidal activity was established with the Mesocricetus auratus model; amebic liver abscess (ALA) development was evaluated by magnetic resonance (MR) and validated post mortem. In vitro, compounds 1 and 2 caused chromatin condensation, intracellular ROS, and loss of actin structures. Coupling analysis showed that they bind to the allosteric and catalytic sites of actin with binding energies of −11.30 and −8.45 kcal/mol, respectively. Treatments with 1 and 2 induced a decrease in ALA formation without toxic effects on the liver and kidney. Thus, compound 1, but not 2, was able to induce apoptosis-like effects in E. histolytica trophozoites by intracellular production of ROS that affected the actin cytoskeleton structuration. In vivo, compound 1 was more active than compound 2 to reduce the development of ALA.

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Section: Resultsmentioning

confidence: 95%

Linearolactone and Kaempferol Disrupt the Actin Cytoskeleton in Entamoeba histolytica: Inhibition of Amoebic Liver Abscess Development

et al. 2020

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“…After an incubation of 24 h at 37 °C and 5% of CO 2 atmosphere, the fluorescence was measured using the EnSpire Multimode Plate Reader® and the CC 50 was calculated using the Graphpad Prism 9.0.0. ( López-Arencibia et al, 2019b ).…”

Section: Methodsmentioning

confidence: 99%

Acrylonitrile derivatives: In vitro activity and mechanism of cell death induction against Trypanosoma cruzi and Leishmania amazonensis

Bethencourt-Estrella,

Delgado-Hernández,

López-Arencibia

et al. 2024

International Journal for Parasitology: Drugs and Drug Resistan

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“…After 15 min of incubation at room temperature, parasites were analyzed. Fluorescence pictures were taken with the EVOS ® FL Cell Imaging System (ThermoFisher Scientific, MA, USA) [48].…”

Section: Plasmatic Membrane Permeability Analysismentioning

confidence: 99%

Acrylonitrile Derivatives against Trypanosoma cruzi: In Vitro Activity and Programmed Cell Death Study

et al. 2021

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The neglected infection known as Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, results in more than 7000 deaths per year, with an increasing number of cases in non-endemic areas such as Europe or the United States. Moreover, with the current available therapy, only two compounds which are active against the acute phase of the disease are readily available. In addition, these therapeutic agents display multiple undesired side effects such as high toxicity, they are expensive, the treatment is lengthy and the resistant strain has emerged. Therefore, there is a need to find new compounds against Chagas disease which should be active against the parasite but also cause low toxicity to the patients. In the present work, the activity of novel acrylonitriles against Trypanosoma cruzi was evaluated as well as the analysis of the physiological events induced in the treated parasites related to the cell death process. Hence, the characteristic features of an apoptosis-like process such as chromatin condensation and mitochondrial membrane potential, among others, were studied. From the 32 compounds tested against the epimastigote stage of T. cruzi, 11 were selected based on their selectivity index to determine if these compounds were able to induce programmed cell death (PCD) in the treated parasites. Furthermore, acrylonitriles Q5, Q7, Q19, Q27 and Q29 were shown to trigger physiological events related in the PCD. Therefore, this study highlights the therapeutic potential of acrylonitriles as novel trypanocidal agents.

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Withanolides from Withania aristata as Antikinetoplastid Agents through Induction of Programmed Cell Death

Cited by 16 publications

References 26 publications

Linearolactone and Kaempferol Disrupt the Actin Cytoskeleton in Entamoeba histolytica: Inhibition of Amoebic Liver Abscess Development

Linearolactone and Kaempferol Disrupt the Actin Cytoskeleton in Entamoeba histolytica: Inhibition of Amoebic Liver Abscess Development

Acrylonitrile derivatives: In vitro activity and mechanism of cell death induction against Trypanosoma cruzi and Leishmania amazonensis

Acrylonitrile Derivatives against Trypanosoma cruzi: In Vitro Activity and Programmed Cell Death Study

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