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

• 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
• Format: Article
• Language: English
• 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
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2021.108100

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.