Antifungal Activity in Compounds from the Australian Desert Plant Eremophila alternifolia with Potency Against Cryptococcus spp.

Abstract

Plant metabolites that have shown activity against bacteria and/or environmental fungi represent valuable leads for the identification and development of novel drugs against clinically important human pathogenic fungi. Plants from the genus Eremophila were highly valued in traditional Australian Aboriginal medicinal practices, and E. alternifolia was the most prized among them. As antibacterial activity of extracts from E. alternifolia has been documented, this study addresses the question whether there is also activity against infectious fungal human pathogens. Compounds from leaf-extracts were purified and identified by 1- and 2-D NMR. These were then tested by disk diffusion and broth microdilution assays against ten clinically and environmentally relevant yeast and mould species. The most potent activity was observed with the diterpene compound, 8,19-dihydroxyserrulat-14-ene against Cryptococcus gattii and Cryptococcus neoformans, with minimum inhibition concentrations (MIC) comparable to those of Amphotericin B. This compound also exhibited activity against six Candida species. Combined with previous studies showing an antibacterial effect, this finding could explain a broad antimicrobial effect from Eremophila extracts in their traditional medicinal usage. The discovery of potent antifungal compounds from Eremophila extracts is a promising development in the search for desperately needed antifungal compounds particularly for Cryptococcus infections.

The biosynthesis of the anti‐microbial diterpenoid leubethanol in Leucophyllum frutescens proceeds via an all‐cis prenyl intermediate

“…Leubethanol from Leucophyllum frutescens is active against multi-drug-resistant tuberculosis ( Molina-Salinas et al ., 2011 ), biflorin from Capraria biflora and Eremophila neglecta has both anti-tumor ( Carvalho et al ., 2013 ) and anti-microbial ( Ndi et al ., 2007a ) properties, and microthecaline A from Eremophila microtheca is active against malaria ( Kumar et al ., 2018 ). While relatively few have been identified in other genera, the Eremophila genus is especially rich in these anti-microbial compounds ( Ndi et al ., 2007b ; Anakok et al ., 2012 ; Barnes et al ., 2013 ; Mon et al ., 2015 ; Algreiby et al ., 2018 ; Hossain et al ., 2019 ) and at least three are found in the Myoporum genus ( Aminimoghadamfarouj and Nematollahi, 2017 ). Given their promise in therapeutic applications, there has been a substantial effort to devise total chemical syntheses ( Best and Wege, 1986 ; Lu et al ., 2013 ; Yu et al ., 2016 ; R. Kumar et al ., 2017 ; Tenneti et al ., 2018 ; Penjarla et al ., 2019 ) as an alternative to extraction and purification from natural sources ( Figure 2 ).…”

Phytochemistry, Medicinal Properties, Bioactive Compounds, and Therapeutic Potential of the Genus Eremophila (Scrophulariaceae)

“…Similarly, a recent study reported that Eremophila alternifolia leaf extracts have substantial antifungal and antibacterial activity against multiple pathogens [13]. That study also demonstrated that the extracts inhibited several important cellular pathways and disrupted membrane integrity in Gram-positive bacterial species.…”

“…Some of those studies have already been summarised in the preceding section. Additionally, a recent study screened E. alternifolia leaf extracts and isolated compounds for antiviral activity and reported substantial activity [13]. The authors tested the extract and isolated compounds using disk diffusion and broth microdilution assays against ten clinically relevant yeast and mould species.…”

Garlic: An Alternative Treatment for Group B Streptococcus

“…Hossain et al ( 44 ) conducted a study to evaluate the antifungal activity of five isolated compounds from Eremophila alternifolia against eight yeast and two mold species. This study is like ours in relation to the method used to determine the MIC of the compounds (in triplicate); for this reason, it was used as a preliminary screening technique for antimicrobial activity.…”