Three New Lindenane Sesquiterpenoids From Lindera aggregata With Selective Antifungal Activity

Area of Science:

• Natural Product Chemistry
• Medicinal Chemistry
• Mycology

Background:

• Candida albicans infections pose a significant global health challenge due to rising drug resistance.
• There is a critical need for novel, selective antifungal agents.
• Lindenane-type sesquiterpenoids from Lindera aggregata are known for diverse bioactivities, but their antifungal potential is underexplored.

Purpose of the Study:

• To isolate and characterize novel lindenane-type sesquiterpenoids from Lindera aggregata.
• To evaluate the antifungal activity of these compounds against Candida albicans.
• To explore the potential of these natural products as new antifungal lead scaffolds.

Main Methods:

• Isolation of compounds from Lindera aggregata roots using chromatographic techniques.
• Structure elucidation via comprehensive spectroscopic analyses (NMR, MS) and Electronic Circular Dichroism (ECD) calculations.
• Antimicrobial assays to determine Minimum Inhibitory Concentrations (MIC) against Candida albicans.

Main Results:

• Three new lindenane-type sesquiterpenoids (1, 2, 4) and fifteen known analogues were isolated.
• Compounds 1-6, 8, 12, and 14 demonstrated potent and selective inhibition against Candida albicans (MIC: 4-8 µg/mL).
• These compounds exhibited minimal or no activity against bacteria, indicating selectivity.

Conclusions:

• The study expands the known structural diversity of lindenane-type sesquiterpenoids.
• Identified compounds represent promising natural lead scaffolds for developing new antifungal agents.
• Lindera aggregata is a valuable source for discovering novel therapeutics against fungal pathogens.