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

Area of Science:

• Natural Product Chemistry
• Parasitology
• Computational Chemistry

Background:

• Chagas disease, caused by Trypanosoma cruzi, remains a significant global health concern.
• Current treatments for Chagas disease have limitations, necessitating the search for novel therapeutic agents.
• Mutisia campanulata Less is a plant species with potential medicinal properties.

Purpose of the Study:

• To isolate and characterize compounds from Mutisia campanulata with trypanocidal activity.
• To evaluate the in vitro and in silico efficacy of a subfraction against Trypanosoma cruzi.
• To investigate the molecular interactions of key compounds with Trypanosoma cruzi enzyme targets.

Main Methods:

• Chromatographic isolation and purification of plant compounds.
• Gas Chromatography-Mass Spectrometry (GC-MS) and 13C Nuclear Magnetic Resonance (NMR) for structural elucidation.
• In vitro assays to determine trypanocidal activity (IC50).
• Molecular docking, molecular dynamics simulations, and MMPBSA analysis for in silico evaluation.

Main Results:

• A subfraction rich in aliphatic hydrocarbons and pentacyclic triterpenes was isolated from Mutisia campanulata.
• The subfraction exhibited significant in vitro trypanocidal activity against Trypanosoma cruzi epimastigote forms (IC50 = 5.88 μg/mL).
• Pseudotaraxasterol showed strong binding affinity to the 4C27 enzyme target of T. cruzi (-10.2 kcal/mol) and stable interactions during molecular dynamics simulations.

Conclusions:

• Pseudotaraxasterol, isolated from Mutisia campanulata, possesses significant trypanocidal activity.
• In silico studies confirm pseudotaraxasterol's potential as a lead compound for Chagas disease drug development.
• Specific amino acid residues (MET-106, LEU-356, TYR-103) are critical for pseudotaraxasterol's binding to the target enzyme.