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Review
. 2024 Aug 21:15:1447450.
doi: 10.3389/fphar.2024.1447450. eCollection 2024.

A review of the fernane-type triterpenoids as anti-fungal drugs

Chun-Yue Liu  1   2 , Lu Zhang  1 , Si-Xuan Liu  1 , Yong-Fu Lu  1 , Chang Li  1 , Yue-Hu Pei  1
Affiliations
Review

A review of the fernane-type triterpenoids as anti-fungal drugs

Chun-Yue Liu et al. Front Pharmacol. .

Abstract

Human fungal pathogens could cause a broad plethora of infections in both the immunocompetent and immunocompromised host. Fungal infections have become important causes of morbidity and mortality in recent years, the current arsenal of anti-fungal therapies was restricted. Ibrexafungerp was a novel, highly bioavailable glucan synthase inhibitor formulated for both intravenous and oral administration being developed by Scynexis; it was also the first novel anti-fungal drug class approved in more than 20 years. Ibrexafungerp was one semi-synthetic derivative of enfumafungin, a natural product isolated from fungi. This review reported the discovery of enfumafungin and ibrexafungerp, their anti-fungal mechanism, summed up 63 fernane-type triterpenoids from natural products, including 49 from plants, 9 from fungi and 5 from lichen. In addition, the review summarized the progress of enzymes responsible for the biosynthesis of type II fernane triterpenoid (enfumafungin skeleton) and type I fernane triterpenoid (polytolypin skeleton). The good example kept our confidence up for searching for new leading compounds and discovering drugs from fungi.

Keywords: anti-fungal; enfumafungin; fernane type; ibrexafungerp; triterpenoid.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The synthetic procedure from enfumafungin to ibrexafungerp.
FIGURE 2
FIGURE 2
Key milestones in the development of oral ibrexafungerp from enfumafungin.
FIGURE 3
FIGURE 3
Fernane type tri-terpenoids (1–11) from natural products.
FIGURE 4
FIGURE 4
Fernane type tri-terpenoids (12–29) from natural products.
FIGURE 5
FIGURE 5
Fernane type tri-terpenoids (30–49) from natural products.
FIGURE 6
FIGURE 6
Fernane type tri-terpenoids (50–63) from natural products.
FIGURE 7
FIGURE 7
Biosynthesis gene cluster of enfumafungin.
FIGURE 8
FIGURE 8
Biosynthesis pathway of polytolypin.
See this image and copyright information in PMC

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