Extended Antimicrobial Profile of Chromone-Butenafine Hybrids

Area of Science:

• Medicinal Chemistry
• Antimicrobial Drug Discovery
• Organic Synthesis

Background:

• Fungal infections pose a global health challenge, exacerbated by antifungal drug resistance.
• Co-infections are common in immunocompromised and hospitalized patients.
• Existing antifungal treatments face limitations due to resistance and toxicity.

Purpose of the Study:

• To design and synthesize novel hybrid compounds combining chromone/xanthone scaffolds with butenafine.
• To evaluate the antimicrobial activity of these hybrid compounds against resistant fungal and bacterial strains.
• To identify promising candidates for further drug development.

Main Methods:

• Synthesis of hybrid molecules linking chromone and xanthone scaffolds to the butenafine moiety via various linkers.
• Antimicrobial susceptibility testing against key fungal pathogens (e.g., *C. auris*, *C. tropicalis*, *C. neoformans*) and Gram-positive bacteria (*S. aureus*).
• Determination of selectivity and therapeutic indexes for active compounds.

Main Results:

• The xanthone-based hybrid compound 3 demonstrated potent activity against drug-resistant *Candida auris*, *Candida tropicalis*, and *Cryptococcus neoformans*.
• Compound 3 also exhibited significant antibacterial efficacy against Gram-positive bacteria, including *Staphylococcus aureus*.
• Compound 3 displayed favorable selectivity and therapeutic indexes (9.1 and >16, respectively).

Conclusions:

• The synthesized xanthone-based compound 3 is a promising prototype for developing new antimicrobial agents.
• Further hit-to-lead optimization of compound 3 is warranted to address resistant fungal and bacterial infections.
• Hybrid molecules incorporating privileged scaffolds offer a viable strategy for overcoming antimicrobial resistance.