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ECB-ART-54384
Biochim Biophys Acta Biomembr 2025 Oct 18;:184477. doi: 10.1016/j.bbamem.2025.184477.
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Exploring the antitrypanosomal activity of viscidone, an acetophenone derivative from Baccharis retusa (Asteraceae), using biomembrane models.

Umehara E , Dos Santos CHT , da Silva LF , Thevenard F , Tempone AG , Rosa ME , Caseli L , Lago JHG .


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This study evaluated the antiprotozoal activity of viscidone, an acetophenone isolated from Baccharis retusa, against trypomastigote forms of Trypanosoma cruzi. Viscidone showed potent antiparasitic effects (EC₅₀ = 21.3 ± 1.4 μM), comparable to benznidazole, and exhibited no cytotoxicity toward NCTC mammalian cells (CC₅₀ > 200 μM), resulting in a selectivity index (SI) higher than 9.4. To explore its mechanism of action, biophysical analyses using DPPE Langmuir monolayers as biomimetic membranes revealed that viscidone strongly interacts with lipid interfaces - expanding monolayers, decreasing compressional and viscoelastic moduli, and inducing microdomain formation, as observed by Brewster angle microscopy. These results indicate that viscidone disrupts PE-rich lipid domains, a hallmark of protozoan membranes. Its ability to insert into lipid layers under high surface pressures and its synergistic behavior with the membrane matrix support membrane perturbation as a likely mechanism underlying its antiparasitic effect. Overall, this multidisciplinary study identifies viscidone as a promising lead for antitrypanosomal drug development and highlights the value of membrane biophysics in antiparasitic research.

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