Abstract
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 Melipona mondury geopropolis from the Bosque da Barra da Tijuca (RJ, Brazil) and evaluated their activity against Trypanosoma cruzi. The extracts were obtained using commercial grain alcohol 96° GL and fractionated with hexane and dichloromethane. The antichagasic activity was determined, with IC(50) values ranging from 4.54 to 53.02 μg/mL. Phytochemical investigation of the dichloromethane fraction resulted in the isolation of two C-methylated flavanones, (2S)-strobopinin and (2S)-cryptostrobin, which were identified for the first time in Brazilian geopropolis. These compounds showed IC(50) 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 C-methylation. The results highlight M. mondury geopropolis as a promising natural source of antiparasitic agents, supporting its potential for drug development.