Characteristics and Adverse Events of Patients for Whom Nifurtimox Was Released Through CDC-Sponsored Investigational New Drug Program for Treatment of Chagas Disease — United States, 2001–2021

Abbott, Andrew P.; Montgomery, Susan P.; Chancey, Rebecca J

doi:10.15585/mmwr.mm7110a2

Cited by 7 publications

(15 citation statements)

References 9 publications

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Section: Discussionmentioning

confidence: 99%

“…Although nitrofuran derivatives are known to cause mutagenic and genotoxic effects [ 16 , 19 ], beneficial effects of a drug of this family have already been proven in the treatment of Chagas disease [ 18 ]. Additionally, only mild adverse effects were observed in humans [ 17 , 18 ]. Therefore, regulatory agencies such as the Food and Drug Administration (FDA) have approved the commercial use of Nifurtimox in the treatment of Chagas disease [ 18 , 85 ].…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, only mild adverse effects were observed in humans [ 17 , 18 ]. Therefore, regulatory agencies such as the Food and Drug Administration (FDA) have approved the commercial use of Nifurtimox in the treatment of Chagas disease [ 18 , 85 ]. Research groups around the world have been carrying out reformulations that make nitrofurans safe for human health and effective against diseases [ 19 , 20 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…Nitrofurans are described as antibiotics with a broad spectrum of action. They have been widely used in veterinary medicine for decades, and there are new drugs in this class approved for the treatment of Chagas disease [ 15 , 16 , 17 , 18 ]. However, due to problems related to toxicity, such as the appearance of mutations and cancers, as well as cases of pulmonary, cardiac, and reproductive system toxicity, hepatotoxicity, and nephrotoxicity, especially in long-term treatments, they have been banned in several countries [ 16 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the Anti-Histoplasma capsulatum Activity of Indole and Nitrofuran Derivatives and Their Pharmacological Safety in Three-Dimensional Cell Cultures

et al. 2022

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Histoplasma capsulatum is a fungus that causes histoplasmosis. The increased evolution of microbial resistance and the adverse effects of current antifungals help new drugs to emerge. In this work, fifty-four nitrofurans and indoles were tested against the H. capsulatum EH-315 strain. Compounds with a minimum inhibitory concentration (MIC90) equal to or lower than 7.81 µg/mL were selected to evaluate their MIC90 on ATCC G217-B strain and their minimum fungicide concentration (MFC) on both strains. The quantification of membrane ergosterol, cell wall integrity, the production of reactive oxygen species, and the induction of death by necrosis–apoptosis was performed to investigate the mechanism of action of compounds 7, 11, and 32. These compounds could reduce the extracted sterol and induce necrotic cell death, similarly to itraconazole. Moreover, 7 and 11 damaged the cell wall, causing flaws in the contour (11), or changing the size and shape of the fungal cell wall (7). Furthermore, 7 and 32 induced reactive oxygen species (ROS) formation higher than 11 and control. Finally, the cytotoxicity was measured in two models of cell culture, i.e., monolayers (cells are flat) and a three-dimensional (3D) model, where they present a spheroidal conformation. Cytotoxicity assays in the 3D model showed a lower toxicity in the compounds than those performed on cell monolayers. Overall, these results suggest that derivatives of nitrofurans and indoles are promising compounds for the treatment of histoplasmosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of the Anti-Histoplasma capsulatum Activity of Indole and Nitrofuran Derivatives and Their Pharmacological Safety in Three-Dimensional Cell Cultures

et al. 2022

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“…A study involving patients with established Chagas cardiomyopathy suggested that Bzn treatment may be less effective in those with chronic CD 9 . Regarding nifurtimox, a CDC report between 2001 and 2021 indicates that the patients’ most common adverse effects were nausea, anorexia, weight loss, headache, and abdominal pain, with some reporting severe adverse events as depression, peripheral neuropathy, paresthaesia, dizziness/vertigo 10 . Moreover, treatment-refractory strains of parasites are frequently observed 11–13 .…”

Section: Introductionmentioning

confidence: 99%

Repurposing of rabeprazole as an anti- Trypanosoma cruzi drug that targets cellular triosephosphate isomerase

García-Torres,

De la Mora-De la Mora,

López-Velázquez

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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Trypanosoma cruzi is the causative agent of American trypanosomiasis, which mainly affects populations in Latin America. Benznidazole is used to control the disease, with severe effects in patients receiving this chemotherapy. Previous studies have demonstrated the inhibition of triosephosphate isomerase from T. cruzi , but cellular enzyme inhibition has yet to be established. This study demonstrates that rabeprazole inhibits both cell viability and triosephosphate isomerase activity in T. cruzi epimastigotes. Our results show that rabeprazole has an IC 50 of 0.4 µM, which is 14.5 times more effective than benznidazole. Additionally, we observed increased levels of methyl-glyoxal and advanced glycation end products after the inhibition of cellular triosephosphate isomerase by rabeprazole. Finally, we demonstrate that the inactivation mechanisms of rabeprazole on triosephosphate isomerase of T. cruzi can be achieved through the derivatization of three of its four cysteine residues. These results indicate that rabeprazole is a promising candidate against American trypanosomiasis.

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Chagas Disease: Epidemiology, Diagnosis, and Treatment

Swett,

Rayes,

Campos

et al. 2024

Curr Cardiol Rep

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Characteristics and Adverse Events of Patients for Whom Nifurtimox Was Released Through CDC-Sponsored Investigational New Drug Program for Treatment of Chagas Disease — United States, 2001–2021

Cited by 7 publications

References 9 publications

Evaluation of the Anti-Histoplasma capsulatum Activity of Indole and Nitrofuran Derivatives and Their Pharmacological Safety in Three-Dimensional Cell Cultures

Evaluation of the Anti-Histoplasma capsulatum Activity of Indole and Nitrofuran Derivatives and Their Pharmacological Safety in Three-Dimensional Cell Cultures

Repurposing of rabeprazole as an anti- Trypanosoma cruzi drug that targets cellular triosephosphate isomerase

Chagas Disease: Epidemiology, Diagnosis, and Treatment

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