<i>C</i>-methylated Flavanones with Antitrypanosomal Activity Isolated of Geopropolis from <i>Melipona mondury</i>

Geopropolis is a natural antibiotic produced by stingless bees, supplemented with earth and clay. Bee products are a promising source of natural bioactive compounds with potential for the development of new drugs for neglected tropical diseases, such as Chagas disease. This study analyzed extracts of <i>Melipona mondury</i> geopropolis from the Bosque da Barra da Tijuca (RJ, Brazil) and evaluated their activity against <i>Trypanosoma cruzi</i>. The extracts were obtained using commercial grain alcohol 96° GL and fractionated with hexane and dichloromethane. The antichagasic activity was determined, with IC₅₀ values ranging from 4.54 to 53.02 μg/mL. Phytochemical investigation of the dichloromethane fraction resulted in the isolation of two <i>C</i>-methylated flavanones, (2<i>S</i>)-strobopinin and (2<i>S</i>)-cryptostrobin, which were identified for the first time in Brazilian geopropolis. These compounds showed IC₅₀ values of 21.21 μM and 21.55 μM, respectively, with distinct cytotoxities: 33.80 μM for strobopinin and 99.79 μM for cryptostrobin. Molecular modeling studies were conducted to propose a mechanism of action on a candidate enzyme target, glyceraldehyde-3-phosphate dehydrogenase, and possible reasons for the selectivity differences caused by <i>C</i>-methylation. The results highlight <i>M. mondury</i> geopropolis as a promising natural source of antiparasitic agents, supporting its potential for drug development.