Activity of β-Caryophyllene Oxide and Benznidazole Mixture Against Trypanosoma cruzi and In Silico Prediction of Anti-Trypanocidal Interaction

Trypanosoma cruzi is the protozoan parasite that causes Chagas disease, affecting approximately 6–7 million people worldwide. The current treatment lacks efficacy in the chronic phase of the disease. This study aims to determine the in vitro synergistic activity of concomitant therapy (benznidazole with β-caryophyllene oxide) against Trypanosoma cruzi, assess its cytotoxicity, and propose the mechanism of this synergism through in silico analysis. The tested concentrations of the treatment demonstrated hemocompatibility (80% cell viability). Additionally, synergistic activity against the parasite was confirmed, reducing epimastigote viability by up to 80%. In this work, in silico analysis revealed that β-caryophyllene oxide also binds to the T. cruzi ABC channel in regions localized to amino acids 108–271 and 399–558, suggesting this interaction could inhibit it. This treatment emerges as a promising candidate for Chagas disease therapy. It lacks cytotoxic and hemolytic activity while exhibiting synergism against the parasite, such as through the inhibition of ABC channels, as suggested in silico.