Lichen Xanthones as Models for New Antifungal Agents

Area of Science:

• Medicinal Chemistry
• Natural Product Chemistry
• Antimicrobial Research

Background:

• Rising threat of multidrug-resistant microorganisms necessitates novel antimicrobial agents.
• Lichen-derived xanthones are known for their antimicrobial properties, serving as inspiration for new drug discovery.

Purpose of the Study:

• To synthesize novel chlorinated xanthones with diverse substitution patterns.
• To evaluate the synthesized compounds for antibacterial and antifungal activities.

Main Methods:

• Preparation of novel chlorinated xanthones using five distinct chlorination methods.
• Antimicrobial screening of synthesized compounds against bacterial and fungal strains.
• Evaluation of synergistic effects of active compounds with existing antifungal drugs.

Main Results:

• Compound 15 demonstrated promising antibacterial activity against *E. faecalis* and *S. aureus*.
• Compound 18 exhibited potent fungistatic and fungicidal activity against clinical dermatophyte strains with MIC values of 4–8 µg/mL.
• Compound 18 showed significant synergy with fluconazole against *T. rubrum* (ΣFIC = 0.289).

Conclusions:

• The study identified novel chlorinated xanthones as potential leads for developing new antibacterial and antifungal therapies.
• Compound 18 is a promising candidate for treating dermatophyte infections, potentially in combination with fluconazole.