Metabolomic profiling and in vivo toxicity of essential oils as promising hits and affordable bioactive agents against Madurella mycetomatis

There is an increasing demand to develop antifungal agents to combat Madurella mycetomatis; the major causative agent of mycetoma. This infection is currently treated by triazoles, antifungal agents with limited efficacy and thereby high morbidity rates [1]. Hence, there is an urgent need to identify novel and affordable fungicidal agents with fewer side effects. A dozen of essential oils (EOs) of taxonomically diverse aromatic medicinal plants were extracted by hydrodistillation followed by GC/MS analysis. EOs were screened for antifungal activity in vitro and for toxicity in vivo on Galleria mellonella larvae model [2]. The biological and chemical data generated were subsequently subjected to chemometric analysis.

Seven fungal cultures from diverse geographical origin were exposed to various concentrations of essential oils ranging from 0.25-0.0039%v/v employing resazurin viability assay [3]. Itraconazole was used as positive control.

Ten out of twelve tested oils exhibited remarkable in vitro antifungal activity (MIC 0.125- 0.0078%v/v) with no toxicity at 0.5-1%v/v. GC/MS analysis identified diverse monoterpenes and sesquiterpenes associated with antifungal activity. Chemometric analysis revealed that the most active essential oil, Croton zambezicus, was clearly separated by chemical data as well as Xylopia aethiopica and Boswellia papyrifera. Some of the identified pure compounds (Β-caryophyl, p-cymene, sabinene, 1,8-cineole, linalool, thymol and borneol) previously exhibited varying degrees of antimycetomal activity as single compounds. Chemometric analysis of the EOs constituents identified by GC/MS coupled with the antimycetomal activity revealed that the following monoterpenes, terpinen-4-ol, n-octyl acetate, p-cymene, 1,8-cineole, α-terpineol and linalool are most likely the active compounds against M. mycetomatis.

• References

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