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Antifungal Activity of Selected Naphthoquinones and Their Synergistic Combination with Amphotericin B Against Cryptococcus neoformans H99

Summary

Researchers tested five compounds called naphthoquinones for their ability to fight a dangerous fungal infection called cryptococcosis. They found that one compound called 2-MNQ works especially well when combined with the standard antifungal drug amphotericin B, making the treatment more effective. This discovery could lead to better treatments for people with weakened immune systems who are vulnerable to this infection.

Background

Cryptococcosis, caused by Cryptococcus neoformans and Cryptococcus gattii, is a significant health concern particularly in immunocompromised patients. Current antifungal treatments including amphotericin B are limited by toxicity, high costs, and emerging resistance. Naphthoquinones represent a promising alternative class with antimicrobial properties.

Objective

To investigate the antifungal activity of five naphthoquinones against nine isolates of Cryptococcus spp. and assess their synergistic effects with amphotericin B using combination therapy approaches.

Results

2-methoxynaphthalene-1,4-dione (2-MNQ) demonstrated the most promising antifungal activity with MIC values of 3.12-12.5 µg/mL. Checkerboard assays revealed synergistic interaction between 2-MNQ and amphotericin B with FICI of 0.27, achieving a 4.17-fold reduction in amphotericin B MIC. The combination showed 94.72% fungal growth inhibition after 48 hours compared to 63.84% for 2-MNQ alone.

Conclusion

2-MNQ and 2,3-DBNQ show potential as antifungal candidates against Cryptococcus spp., with 2-MNQ demonstrating particularly strong synergistic interactions with amphotericin B. These findings support further preclinical investigation of combination therapies and highlight the importance of structural modifications in naphthoquinones for enhancing antifungal activity and overcoming drug resistance.
  • Published in:Antibiotics (Basel),
  • Study Type:In Vitro Experimental Study,
  • Source: PMID: 40558192, DOI: 10.3390/antibiotics14060602
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