Sedaxicenes: potential new antifungal ferrocene-based agents?

Area of Science:

• Medicinal Chemistry
• Mycology
• Organometallic Chemistry

Background:

• Fungal infections pose a global health challenge with increasing drug resistance.
• Limited research exists for novel antifungal agents.
• Ferrocene derivatives have shown potential in antimalarial and anticancer applications.

Purpose of the Study:

• To synthesize novel ferrocene-based antifungal agents by derivatizing the fungicide sedaxane.
• To evaluate the antifungal activity and toxicity of these new compounds.
• To investigate the mechanism of action, particularly the role of redox activity.

Main Methods:

• Synthesis of ferrocenyl sedaxane derivatives (Sedaxicenes) and a ruthenocene analogue.
• Characterization using analytical techniques and X-ray crystallography.
• Assessment of cytotoxicity against human cells and antifungal activity against fungi.
• Measurement of reactive oxygen species (ROS) levels.

Main Results:

• Sedaxicene derivatives exhibited low toxicity to human cells.
• One derivative showed significant antifungal activity (IC50 = 43 μM).
• The ruthenocene analogue increased ROS levels in yeast, indicating a potential redox-mediated mechanism.

Conclusions:

• Ferrocene and ruthenocene derivatives of sedaxane represent a new class of potential antifungal agents.
• The observed antifungal activity may be linked to a redox-mediated mechanism involving ROS generation.
• Further research into metal-based antifungals is warranted to address drug resistance.