Trypanocidal Effects of Polyprenylated Benzophenone Enriched Brazilian Red Propolis Extract and Its Isolated Constituent

ABSTRACT Chagas disease, a neglected tropical disease, affects millions of individuals in developing countries. Due to the limitations of current therapeutic options, the search for new bioactive compounds is crucial. Brazilian red propolis, a resinous bee product from northeastern Brazil, is recognized for its diverse chemical constituents and biological, including antiparasitic, activities. This study evaluated the in vitro activity of a polyprenylated benzophenone‐enriched Brazilian red propolis extract ( SEBz ) and its constituents, the mixture of isomers guttiferone E and xanthochymol ( GUT/XAN ), and oblongifolin B ( OBL ), against Trypanosoma cruzi (Y strain) trypomastigote and amastigote forms. Cytotoxicity and hemolysis assays assess safety. SEBz exhibited antiparasitic activity, with 50% effective concentration (EC 50 ) values of 17.97 µg mL −1 (trypomastigotes) and 6.83 µg mL −1 (amastigotes) after 48 h, while demonstrating moderate cytotoxicity on the C2C12 myoblast cell line (50% cytotoxicity concentration [CC 50 ] 42.80 µg mL −1 at 48 h). Both GUT/XAN and OBL showed trypanocidal effects (EC 50 ≤ 5 µM against trypomastigotes; GUT/XAN EC 50 7.91 µM on amastigotes), with moderate cytotoxicity (CC 50 < 20 µM). Neither the extract nor the compounds induced significant hemolysis. Ultrastructural analysis of treated parasites revealed nuclear deformation and vacuolation. These findings support the potential of Brazilian red propolis benzophenones as promising leads for Chagas disease drug development.