Exploring therapeutic approaches against Naegleria fowleri infections through the COVID box

Chao-Pellicer, Javier; Arberas-Jiménez, Iñigo; Sifaoui, Ines; Piñero, José E.; Lorenzo-Morales, Jacob

doi:10.1016/j.ijpddr.2024.100545

Cited by 1 publication

(2 citation statements)

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“…Terconazole, known to be one of the most effective triazoles against Candida species, has been reported to exhibit further biological activities (including Trypanosoma cruzi ) and to enhance the activity of antimitotic drugs by inducing apoptosis and G2 arrest in cancer cells [ 20 , 21 , 22 ]. In a previous work, we reported the activity of Terconazole against Naegleria fowleri with an IC 50 of 3.68 ± 0.61 µM [ 13 ]. Despite all the articles that have reported the antifungal activity of various azoles, only a few have shown the mechanism of cell death.…”

Section: Discussionmentioning

confidence: 99%

“…Over 200 research group have evaluated the boxes against various diseases such as cancer and microbial infections, including Leishmania , Acanthamoeba , and Toxoplasma gondii [ 5 , 9 , 10 , 11 ]. The last box has been tested to discover a potent drug against the coronavirus and other pathogens like Toxoplasma gondii and Naegleria fowleri [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Amoebicidal Effect of COVID Box Molecules against Acanthamoeba: A Study of Cell Death

Sifaoui,

Rodríguez-Expósito,

Reyes-Batlle

et al. 2024

Pharmaceuticals

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Acanthamoeba spp. can cause a sight threatening disease. At present, the current treatments used to treat Acanthamoeba spp. Infections, such as biguanide-based antimicrobials, remain inefficacious, with the appearance of resistant forms and high cytotoxicity to host cells. In this study, an initial screening was conducted against Acanthamoeba castellanii Neff and murine macrophages J774A.1 using alamarBlue™. Among the 160 compounds included in the cited box, 90% exhibited an inhibition of the parasite above 80%, while only 18.75% of the compounds inhibited the parasite with a lethality towards murine macrophage lower than 20%. Based on the amoebicidal activity, the cytotoxicity assay, and availability, Terconazole was chosen for the elucidation of the action mode in two clinical strains, Acanthamoeba culbertsoni and Acanthamoeba castellanii L10. A fluorescence image-based system and proteomic techniques were used to investigate the effect of the present azole on the cytoskeleton network and various programmed cell death features, including chromatin condensation and mitochondria dysfunction. Taking all the results together, we can suggest that Terconazole can induce programmed cell death (PCD) via the inhibition of sterol biosynthesis inhibition.

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