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

Summary

Researchers tested sandalwood oil components against a fungal disease called eumycetoma that causes serious skin infections, especially in tropical regions. They found that one component called (Z)-α-santalol was highly effective at killing the fungus and extending survival in laboratory-infected moth larvae, while actually being relatively safe. This natural compound shows promise as a potential new treatment for this neglected disease that currently relies on expensive drugs that are only 40% effective.

Background

Mycetoma is a neglected tropical disease caused by bacteria or filamentous fungi, with eumycetoma caused by Madurella mycetomatis affecting over 80% of patients in the lower limbs. Current treatment with itraconazole is only approximately 40% effective, prompting investigation of alternative therapeutic agents. Sandalwood essential oils have demonstrated antifungal activity against various pathogenic fungi including M. mycetomatis.

Objective

To evaluate the in vivo efficacy and toxicity of (Z)-α-santalol and (Z)-β-santalol, the major sesquiterpene components of Royal Hawaiian sandalwood essential oil, against M. mycetomatis using the Galleria mellonella larvae infection model.

Results

(Z)-α-santalol demonstrated superior in vitro activity (MIC 27.5 µg/mL) compared to (Z)-β-santalol (MIC 55 µg/mL) across all M. mycetomatis strains tested. In vivo, (Z)-α-santalol significantly prolonged larval survival (p=0.014) with minimal toxicity, while (Z)-β-santalol showed toxicity at higher concentrations and the crude essential oil showed no significant benefit, likely due to opposing effects of the two isomers.

Conclusion

(Z)-α-santalol exhibits promising in vivo activity against M. mycetomatis with a favorable therapeutic profile combining potent antifungal activity and minimal toxicity. These findings support further development of purified (Z)-α-santalol as a potential natural antimycetomal agent, with additional studies needed to elucidate mechanisms of action and evaluate efficacy in mammalian models.
  • Published in:Molecules,
  • Study Type:In Vitro and In Vivo Experimental Study,
  • Source: PMID: 41157109, DOI: 10.3390/molecules30204090
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