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Furan derivatives impair proliferation and affect ultrastructural organization of Trypanosoma cruzi and Leishmania amazonensis

Chagas disease and leishmaniasis are neglected diseases caused by parasites of the Trypanosomatidae family and together they affect millions of people in the five continents. The treatment of Chagas disease is based on benznidazole, whereas for leishmaniasis few drugs are available, such as amphoter...

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Published in:Experimental parasitology 2021-05, Vol.224, p.108100, Article 108100
Main Authors: Zuma, Aline Araujo, Teixeira de Macedo-Silva, Sara, Achari, Anushree, Vinayagam, Jayaraman, Bhattacharjee, Pinaki, Chatterjee, Sourav, Gupta, Vivek Kumar, Cristina de Sousa Leite, Amanda, Souza de Castro, Lucas, Jaisankar, Parasuraman, de Souza, Wanderley
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container_title Experimental parasitology
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creator Zuma, Aline Araujo
Teixeira de Macedo-Silva, Sara
Achari, Anushree
Vinayagam, Jayaraman
Bhattacharjee, Pinaki
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Gupta, Vivek Kumar
Cristina de Sousa Leite, Amanda
Souza de Castro, Lucas
Jaisankar, Parasuraman
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description Chagas disease and leishmaniasis are neglected diseases caused by parasites of the Trypanosomatidae family and together they affect millions of people in the five continents. The treatment of Chagas disease is based on benznidazole, whereas for leishmaniasis few drugs are available, such as amphotericin B and miltefosine. In both cases, the current treatment is not entirely efficient due to toxicity or side effects. Encouraged by the need to discover valid targets and new treatment options, we evaluated 8 furan compounds against Trypanosoma cruzi and Leishmania amazonensis, considering their effects against proliferation, infection, and ultrastructure. Many of them were able to impair T. cruzi and L. amazonensis proliferation, as well as cause ultrastructural alterations, such as Golgi apparatus disorganization, autophagosome formation, and mitochondrial swelling. Taken together, the results obtained so far make these compounds eligible for further steps of chemotherapy study. [Display omitted] •Furan derivatives are effective against pathogenic parasites proliferation.•Intracellular amastigote population decreased after treatment.•Furan derivatives led to unpacking of nuclear and mitochondrial DNA.•Loss of typical cell morphology was frequently observed.
doi_str_mv 10.1016/j.exppara.2021.108100
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subjects Cell Line
Chagas Disease - drug therapy
Chagas Disease - parasitology
Chemotherapy
Chromatography, Thin Layer
Endemic Diseases
Furan derivatives
Furans - chemistry
Furans - pharmacology
Humans
Inhibitory Concentration 50
Leishmania amazonensis
Leishmania mexicana - drug effects
Leishmania mexicana - growth & development
Leishmania mexicana - ultrastructure
Leishmaniasis, Cutaneous - drug therapy
Leishmaniasis, Cutaneous - parasitology
Macrophages
Magnetic Resonance Spectroscopy
Microscopy, Electron, Scanning
Molecular Docking Simulation
Neglected Diseases - drug therapy
Neglected Diseases - parasitology
Trypanosoma cruzi
Trypanosoma cruzi - drug effects
Trypanosoma cruzi - growth & development
Trypanosoma cruzi - ultrastructure
Ultrastructure
title Furan derivatives impair proliferation and affect ultrastructural organization of Trypanosoma cruzi and Leishmania amazonensis
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