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

In continuation of our recent report on the in vitro activity of sandalwood essential oils and their major components, the sesquiterpenes (<i>Z</i>)-α- and -β-santalols, against the pathogenic fungus <i>Madurella mycetomatis</i>, causative agent of the neglected tropical disease eumycetoma, we have now tested these isolated constituents, as well as native Royal Hawaiian sandalwood essential oil obtained from <i>Santalum paniculatum</i>, for in vivo activity in a model system using infected <i>Galleria mellonella</i> larvae. Besides confirming the superior activity of (<i>Z</i>)-α-santalol over the (<i>Z</i>)<i>-</i>β-isomer and the crude essential oil in two further strains of <i>M. mycetomatis</i> in vitro, the former compound also turned out to extend the lifespan of the infected larvae significantly, in contrast to (<i>Z</i>)-β-santalol, the total oil, or the antifungal drug itraconazole. The present findings not only characterize (<i>Z</i>)-α-santalol as a natural compound with promising in vivo activity against eumycetoma but also inspire further studies as a potential for novel, more effective therapy and warranting further studies to understand its mechanism of action and potential clinical applications.