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Sandalwood Sesquiterpene (Z)-α-Santalol Exhibits In Vivo Efficacy Against Madurella mycetomatis in Galleria mellonella Larvae

Summary

Researchers tested sandalwood compounds against a fungal infection that causes a tropical disease called eumycetoma. Using a laboratory model with wax moth larvae infected with the fungus, they found that a specific compound called (Z)-α-santalol significantly extended the survival of infected larvae. This compound was more effective than current antifungal drugs and showed promise as a potential new treatment for this neglected tropical disease.

Background

Eumycetoma is a neglected tropical disease caused by Madurella mycetomatis with limited treatment options. Current antifungal therapy using itraconazole is only about 40% effective and often results in suboptimal outcomes. Sandalwood essential oils have previously demonstrated antifungal activity against various pathogenic fungi including M. mycetomatis.

Objective

To evaluate the in vivo efficacy of isolated santalol sesquiterpenes and Royal Hawaiian sandalwood essential oil against M. mycetomatis using the Galleria mellonella larvae model. The study aimed to determine which compound exhibited superior antifungal activity and minimal toxicity for potential therapeutic development.

Results

(Z)-α-santalol demonstrated superior in vitro activity with consistent MIC values of 27.5 µg/mL across all three M. mycetomatis strains tested. In the G. mellonella model, (Z)-α-santalol at the highest concentration significantly prolonged larval survival (p=0.014) compared to untreated controls, while (Z)-β-santalol and itraconazole showed no significant survival benefit.

Conclusion

(Z)-α-santalol exhibits promising in vivo antifungal efficacy against M. mycetomatis with minimal toxicity, positioning it as a potential candidate for novel eumycetoma therapy. Further studies are needed to understand its mechanism of action and evaluate efficacy in mammalian models, though the results suggest advantages over current first-line antifungal treatments.
  • Published in:Molecules,
  • Study Type:In Vitro and In Vivo Experimental Study,
  • Source: 10.3390/molecules30204090, PMID: 41157109
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