Broad-spectrum antifungal activities and mechanism of drimane sesquiterpenoids

Edouarzin, Edruce; Horn, Connor; Paudyal, Anuja; Zhang, Cunli; Lu, Jianyu; Tong, Zongbo; Giaever, Guri; Nislow, Corey; Veerapandian, Raja; Hua, Duy H.; Vediyappan, Govindsamy

doi:10.15698/mic2020.06.719

Cited by 18 publications

(19 citation statements)

References 59 publications

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“…Natural sources, especially plants, are often exposed to pathogens or pests, and thus develop natural defenses against them by producing antimicrobial compounds. We have identified antifungal compounds earlier from medicinal plant-derived compounds and synthetic derivatives [ 15 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…Fungal strains ( C. albicans , C. krusei , C. glabrata , C. auris , and Cryp. neoformans ) [ 31 ] were grown on YPD medium (1% yeast extract, 2% peptone, 2% glucose) before using them for antifungal screening or test assays. The cultures were adjusted to required cell densities (1 × 10 6 /mL) in buffered RPMI 1640 medium with 50 mM glucose according to the CLSI method for yeasts [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

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Anticapsular and Antifungal Activity of α-Cyperone

Horn

Vediyappan

2021

Antibiotics

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Fungal infections affect 300 million people and cause 1.5 million deaths globally per year. With the number of immunosuppressed patients increasing steadily, there is an increasing number of patients infected with opportunistic fungal infections such as infections caused by the species of Candida and Cryptococcus. In fact, the drug-resistant Can. krusei and the emerging pan-antifungal resistant Can. auris pose a serious threat to human health as the existing limited antifungals are futile. To further complicate therapy, fungi produce capsules and spores that are resistant to most antifungal drugs/host defenses. Novel antifungal drugs are urgently needed to fill unmet medical needs. From screening a collection of medicinal plant sources for antifungal activity, we have identified an active fraction from the rhizome of Cyperus rotundus, the nut grass plant. The fraction contained α-Cyperone, an essential oil that showed fungicidal activity against different species of Candida. Interestingly, the minimal inhibitory concentration of α-Cyperone was reduced 8-fold when combined with a clinical antifungal drug, fluconazole, indicating its antifungal synergistic potential and could be useful for combination therapy. Furthermore, α-Cyperone affected the synthesis of the capsule in Cryp. neoformans, a causative agent of fungal meningitis in humans. Further work on mechanistic understanding of α-Cyperone against fungal virulence could help develop a novel antifungal agent for drug-resistant fungal pathogens.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Anticapsular and Antifungal Activity of α-Cyperone

Horn

Vediyappan

2021

Antibiotics

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“…Eight drimane sesquiterpenoids including (−)-drimenol and (+)-albicanol were synthesized from (+)-sclareolide and evaluated for their antifungal activities. (−)-Drimenol ( Figure 23 ) proved to limit the growth of C. auris better than fluconazole in the same concentration [ 134 ]. This natural compound also protected C. elegans from death in a candiasis model [ 134 ].…”

Section: Traditional Medicines and Natural Compoundsmentioning

confidence: 99%

“…(−)-Drimenol ( Figure 23 ) proved to limit the growth of C. auris better than fluconazole in the same concentration [ 134 ]. This natural compound also protected C. elegans from death in a candiasis model [ 134 ].…”

Section: Traditional Medicines and Natural Compoundsmentioning

confidence: 99%

Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris

et al. 2021

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Invasive fungal infections represent an expanding threat to public health. During the past decade, a paradigm shift of candidiasis from Candida albicans to non-albicans Candida species has fundamentally increased with the advent of Candida auris. C. auris was identified in 2009 and is now recognized as an emerging species of concern and underscores the urgent need for novel drug development strategies. In this review, we discuss the genomic epidemiology and the main virulence factors of C. auris. We also focus on the different new strategies and results obtained during the past decade in the field of antifungal design against this emerging C. auris pathogen yeast, based on a medicinal chemist point of view. Critical analyses of chemical features and physicochemical descriptors will be carried out along with the description of reported strategies.

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“…In order to acutely overcome resistance development, new putative antifungal agents should preferably inhibit mechanisms that are known to confer resistance and/or target pathways that differ from those that are already engaged by commercially available medications (mostly involving the cell wall or the plasma membrane). An example of such efforts can be found in the current issue of Microbial Cell, in which Edouarzin and colleagues identified a compound (drimenol, a sesquiterpenoid primary alcohol) that provides a promising starting point for the development of a novel antimycotic [18]. Among the tested drimane sesquiterpenoids, drimenol exhibited the most potent activity against different pathogenic fungi and was also active against fluconazole-resistant strains and C. auris.…”

mentioning

confidence: 99%