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

Summary

Scientists tested five synthetic compounds called naphthoquinones to see if they could fight a serious fungal infection called cryptococcosis. They found that one compound called 2-MNQ worked well against the fungus and was even more effective when combined with a standard antifungal drug (amphotericin B). The combination was strong enough to potentially allow lower doses of the existing drug, which could reduce side effects while improving treatment outcomes.

Background

Cryptococcosis caused by Cryptococcus neoformans and C. gattii remains a significant health concern particularly among immunocompromised patients. Current antifungal treatments like amphotericin B face limitations due to toxicity, costs, and emerging resistance. Naphthoquinones show promise as alternative antimicrobial agents with potential synergistic properties.

Objective

To investigate the antifungal activity of five naphthoquinones against nine Cryptococcus spp. isolates and assess their synergistic effects with amphotericin B. The study aimed to identify promising compound combinations with enhanced efficacy and reduced toxicity for potential use in cryptococcosis treatment.

Results

2-methoxynaphthalene-1,4-dione (2-MNQ) demonstrated 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, reducing the MIC of amphotericin B by 4.17-fold. The combination achieved 94.72% fungal growth inhibition at 48 hours compared to 63.84% for 2-MNQ alone.

Conclusion

Synthetic naphthoquinones, particularly 2-MNQ and 2,3-DBNQ, demonstrate potential as effective antifungal agents against Cryptococcus spp. with synergistic properties when combined with amphotericin B. These findings support the importance of structural modifications in naphthoquinones and highlight the potential of combination therapies for improving cryptococcosis treatment in immunocompromised patients.
  • Published in:Antibiotics (Basel),
  • Study Type:In Vitro Experimental Study,
  • Source: 10.3390/antibiotics14060602, PMID: 40558192
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