Structure Revisions of Phenolic Bisabolane Sesquiterpenes and a Ferroptosis Inhibitor from the Marine-Derived Fungus Aspergillus versicolor YPH93

Abstract

Seven new phenolic bisabolane sesquiterpenoids (1–7), along with 10 biogenetically related analogues (8–17), were obtained from the deep-sea-derived fungus Aspergillus versicolor YPH93. The structures were elucidated based on extensive analyses of the spectroscopic data. Compounds 1–3 are the first examples of phenolic bisabolanes that contain two hydroxy groups attached to the pyran ring. The structures of sydowic acid derivatives (1–6 and 8–10) were carefully studied, leading to the structure revisions of six known analogues, including a revision of the absolute configuration for sydowic acid (10). All metabolites were evaluated for their effects on ferroptosis. Compound 7 exerted inhibition on erastin/RSL3-induced ferroptosis with EC50 values ranging from 2 to 4 μM, while it exhibited no effects on TNFα-induced necroptosis or H2O2-induced cell necrosis.

Identification of a marine‐derived sesquiterpenoid, Compound‐8, that inhibits tumour necrosis factor‐induced cell death by blocking complex II assembly

“…To adapt to such extreme environments, ocean‐derived microorganisms must develop special metabolic mechanisms against cell death induced by harsh environment. It is worthwhile noting that several ferroptosis inhibitors have been identified from the secondary metabolites of marine‐derived fungi (Hao et al, 2023; Li et al, 2023). Our study indicates that the metabolites of marine‐derived fungi also exhibit anti‐necroptosis activity.…”

Ferroptosis inhibitors: past, present and future

“…In recent years, researchers have isolated seven abolane-type sesquiterpenoids (PBSs) from the deep sea fungus Aspergillus floridus YPH1 (Li et al, 2023b), with compound 7 showing a selective inhibitory effect on Erastin/RSL3-induced ferroptosis Frontiers in Pharmacology frontiersin.org 13 similar to Fer-1. However, unlike Fer-1, compound 7 exhibited negligible radical scavenging activity in 2,2-diphenyl-1picrylhydrazyl (DPPH) assays (Li et al, 2023b).…”

“…In recent years, researchers have isolated seven abolane-type sesquiterpenoids (PBSs) from the deep sea fungus Aspergillus floridus YPH1 (Li et al, 2023b), with compound 7 showing a selective inhibitory effect on Erastin/RSL3-induced ferroptosis Frontiers in Pharmacology frontiersin.org 13 similar to Fer-1. However, unlike Fer-1, compound 7 exhibited negligible radical scavenging activity in 2,2-diphenyl-1picrylhydrazyl (DPPH) assays (Li et al, 2023b). Additionally, PBSs25 gossypol acetic acid (GAA) was found to protect cardiomyocytes from ferroptosis in vitro by reducing chelated iron and lipid peroxidation.…”

Ergone Derivatives from the Deep-Sea-Derived Fungus Aspergillus terreus YPGA10 and 25,28-Dihydroxyergone-Induced Apoptosis in Human Colon Cancer SW620 Cells

“…44 Research has shown that inhibiting ferroptosis is a potential therapeutic strategy for patients with either acute single or multiorgan dysfunction. 45 In our search for natural ferroptosis inhibitors, 25 the tested compounds above were also evaluated for the ability to inhibit RSL3-induced ferroptosis in U937 cells at a concentration of 50 μM (Figure 7A). Compound 9 exhibited weak inhibitory activity with an EC 50 value of 30 μM (Figure S87).…”

“…Steroids identified from fungi are highly functionalized and display diverse activities, − attracting considerable attention from natural product chemists. Ergone, an ergosterol derivative characterized by a highly conjugated system (a 4,6,8(14)-trien-3-one unit), is a major metabolite of several medicinal macrofungi ( Ganoderma lucidum , Polyporus umbellatus ) and has demonstrated to possess biological activities including antitumor, diuresis, immunosuppression, and antidiabetic properties. , As part of our ongoing efforts to discover cytotoxic molecules from deep-sea-derived fungi, − a Sephadex LH-20 fraction of the EtOAc extract of Aspergillus terreus YPGA10 showed inhibition of 68% toward the SW620 cell line, while showing negligible effects against four other tumor cell lines at a concentration of 100 μg/mL. The DAD-HPLC chromatogram of this fraction showed a series of peaks with similar UV absorptions at 202 and 336 nm, indicating the presence of congeners with a similar conjugated system.…”