A Review of the Fernane-type Triterpenoids As Anti-fungal Drugs

Overview

Journal Front Pharmacol

Date 2024 Sep 5

PMID 39234110

Authors

Chun-Yue Liu

Lu Zhang

Si-Xuan Liu

Yong-Fu Lu

Chang Li

Yue-Hu Pei

Affiliations

Soon will be listed here.

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.

References

Pfaller M, Messer S, Motyl M, Jones R, Castanheira M . Activity of MK-3118, a new oral glucan synthase inhibitor, tested against Candida spp. by two international methods (CLSI and EUCAST). J Antimicrob Chemother. 2012; 68(4):858-63. DOI: 10.1093/jac/dks466. View

Elander R . Industrial production of beta-lactam antibiotics. Appl Microbiol Biotechnol. 2003; 61(5-6):385-92. DOI: 10.1007/s00253-003-1274-y. View

Schwebke J, Sobel R, Gersten J, Sussman S, Lederman S, Jacobs M . Ibrexafungerp Versus Placebo for Vulvovaginal Candidiasis Treatment: A Phase 3, Randomized, Controlled Superiority Trial (VANISH 303). Clin Infect Dis. 2021; 74(11):1979-1985. PMC: 9187327. DOI: 10.1093/cid/ciab750. View

Deyrup S, Gloer J, ODonnell K, Wicklow D . Kolokosides A-D: triterpenoid glycosides from a Hawaiian isolate of Xylaria sp. J Nat Prod. 2007; 70(3):378-82. DOI: 10.1021/np060546k. View

Hamed A, Masullo M, Pecio L, Gallotta D, Mahalel U, Pawelec S . Unusual fernane and gammacerane glycosides from the aerial parts of Spergula fallax. J Nat Prod. 2014; 77(3):657-62. DOI: 10.1021/np4008415. View

Phillips N, Rocktashel M, Merjanian L . Ibrexafungerp for the Treatment of Vulvovaginal Candidiasis: Design, Development and Place in Therapy. Drug Des Devel Ther. 2023; 17:363-367. PMC: 9921437. DOI: 10.2147/DDDT.S339349. View

Sobel J . Vulvovaginal candidosis. Lancet. 2007; 369(9577):1961-71. DOI: 10.1016/S0140-6736(07)60917-9. View

Wang X, Zhang H, Ren D, Ji M, Yu W, Lou H . Lobarialides A-C, antifungal triterpenoids from the lichen Lobaria kurokawae. Chem Biodivers. 2009; 6(5):746-53. DOI: 10.1002/cbdv.200800054. View

Hector R, Bierer D . New β-glucan inhibitors as antifungal drugs. Expert Opin Ther Pat. 2011; 21(10):1597-610. DOI: 10.1517/13543776.2011.603899. View

10.

Perlin D . Current perspectives on echinocandin class drugs. Future Microbiol. 2011; 6(4):441-57. PMC: 3913534. DOI: 10.2217/fmb.11.19. View

11.

Pfaller M, Messer S, Rhomberg P, Borroto-Esoda K, Castanheira M . Differential Activity of the Oral Glucan Synthase Inhibitor SCY-078 against Wild-Type and Echinocandin-Resistant Strains of Candida Species. Antimicrob Agents Chemother. 2017; 61(8). PMC: 5527608. DOI: 10.1128/AAC.00161-17. View

12.

Angulo D, Alexander B, Rautemaa-Richardson R, Alastruey-Izquierdo A, Hoenigl M, Ibrahim A . Ibrexafungerp, a Novel Triterpenoid Antifungal in Development for the Treatment of Mold Infections. J Fungi (Basel). 2022; 8(11). PMC: 9695964. DOI: 10.3390/jof8111121. View

13.

Chavez M, Garcia A, Lee H, Lau G, Parker E, Komnick K . Synthesis of Fusidic Acid Derivatives Yields a Potent Antibiotic with an Improved Resistance Profile. ACS Infect Dis. 2021; 7(2):493-505. PMC: 8713577. DOI: 10.1021/acsinfecdis.0c00869. View

14.

Newman D, Cragg G . Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019. J Nat Prod. 2020; 83(3):770-803. DOI: 10.1021/acs.jnatprod.9b01285. View

15.

Sobel J, Borroto-Esoda K, Azie N, Angulo D . pH Activity of Ibrexafungerp against Fluconazole-Susceptible and -Resistant Isolates from Women with Vulvovaginal Candidiasis. Antimicrob Agents Chemother. 2021; 65(8):e0056221. PMC: 8284466. DOI: 10.1128/AAC.00562-21. View

16.

Waterer G . Advances in anti-fungal therapies. Mycopathologia. 2021; 186(5):665-672. PMC: 8280599. DOI: 10.1007/s11046-021-00560-2. View

17.

Colombo R, Vazquez J . An evaluation of ibrexafungerp for the treatment of invasive candidiasis: the evidence to date. Expert Opin Pharmacother. 2021; 22(7):797-807. DOI: 10.1080/14656566.2021.1890026. View

18.

Sun L, Sun S, Cheng A, Wu X, Zhang Y, Lou H . In vitro activities of retigeric acid B alone and in combination with azole antifungal agents against Candida albicans. Antimicrob Agents Chemother. 2009; 53(4):1586-91. PMC: 2663064. DOI: 10.1128/AAC.00940-08. View

19.

Yuan X, Xu G, Wu W, Yang T, Li G . Peniciside, a new triterpenoid glycoside, from the fungus Penicillium sp. 169. Arch Pharm Res. 2012; 35(2):311-4. DOI: 10.1007/s12272-012-0210-z. View

20.

Onishi J, Meinz M, Thompson J, Curotto J, Dreikorn S, Rosenbach M . Discovery of novel antifungal (1,3)-beta-D-glucan synthase inhibitors. Antimicrob Agents Chemother. 2000; 44(2):368-77. PMC: 89685. DOI: 10.1128/AAC.44.2.368-377.2000. View