Antimalarial Eudesmane Sesquiterpenoids from Dobinea delavayi

Area of Science:

• Natural Products Chemistry
• Medicinal Chemistry
• Pharmacology

Background:

• The roots of Dobinea delavayi are a source of diverse sesquiterpenoids.
• Sesquiterpenoids are known for various biological activities, including antimalarial properties.

Purpose of the Study:

• To isolate and characterize new sesquiterpenoids from Dobinea delavayi roots.
• To evaluate the antimalarial activity of isolated compounds against Plasmodium yoelii.
• To elucidate the potential mechanism of action for active compounds.

Main Methods:

• Isolation and purification of compounds using chromatographic techniques.
• Structure elucidation through comprehensive spectroscopic data (NMR, MS) and single-crystal X-ray diffraction.
• In vitro antimalarial activity assay against Plasmodium yoelii BY265RFP.
• Assessment of mitochondrial membrane potential and reactive oxygen species (ROS) production.

Main Results:

• Eleven new angeloylated eudesmane sesquiterpenoids (dobinins D-N) and four known compounds were isolated.
• Dobaczins K-N represent novel noreudesmane analogues with a unique 6/5-fused skeleton.
• Compound 12 exhibited significant antimalarial activity (59.1% inhibition), outperforming artemisinin.
• Compounds 3, 5, and 15 showed moderate antimalarial activity (14.5%-18.5% inhibition).
• Compound 12 induced apoptosis in Plasmodium yoelii via mitochondrial depolarization and ROS production, potentially mediated by IL-12 and IFN-γ.

Conclusions:

• Dobinea delavayi is a rich source of structurally unique sesquiterpenoids.
• Compound 12 is a promising lead compound for antimalarial drug development due to its potent activity and novel mechanism.
• The proposed biosynthetic pathway provides insights into the formation of these unique sesquiterpenoids.