In Vitro and In Silico Evaluation of the Trypanocidal Activity of a Subfraction Isolated from Mutisia campanulata

In the present study, a subfraction rich in aliphatic hydrocarbons and pentacyclic triterpenes was isolated after chromatographic steps from Mutisia campanulata Less and its trypanocidal activity were evaluated using in vitro and in silico approaches. The chemical structures of the compounds present in the subfraction were defined by GC-MS and ¹³C NMR data analysis. The trypanocidal activity in vitro of the subfraction indicated potency against epimastigote forms of the Y strain from Trypanosoma cruzi (IC₅₀ of 5.88 ± 0.13 μg/mL). Molecular docking studies were conducted using four T. cruzi enzyme targets (1TC1, 1YHL, 2EF6 and 4C27) and six compounds, including a control. The pseudotaraxasterol obtained better results with an energy of -10.2 kcal/mol for the 4C27 enzyme. The RMSD trajectory of the pseudotaraxasterol in protein-ligand complex indicates stability during the 100 ns molecular dynamics simulation and several weak van der Waals interactions predominate in protein-ligand interactions. MMPBSA-per-residue decomposition analysis was used to provide insight into the interactions between the binding site and the pseudotaraxasterol. The findings revealed that the amino acid residues MET-106, LEU-356, and TYR-103 play a critical role in effective binding interactions. Therefore, pseudotaraxasterol holds potential for the development of new prototypes for the treatment of Chagas disease.