Exploring the antitrypanosomal activity of viscidone, an acetophenone derivative from Baccharis retusa (Asteraceae),...

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.