Luwei He

Stucturally Diverse Sesquiterpenes Produced by a Chinese Tibet Fungus Stereum hirsutum and Their Cytotoxic and Immunosuppressant Activities

Two new heterodimeric sesquiterpenes, sterhirsutins C (1) and D (2), along with eight new sesquiterpenoid derivatives, sterhirsutins E--L (3-10), were isolated from the culture of Stereum hirsutum. The absolute configuration of 1 was assigned by a single-crystal X-ray diffraction experiment. Compounds 1 and 2 possessed an unprecedented chemical skeleton with a 5/5/5/6/9/4 fused ring system. Compound 10 is the first sesquiterpene coupled with a xanthine moiety. Compounds 1-10 showed cytotoxicity against K562 and HCT116 cell lines. Compound 9 induced autophagy in HeLa cells. Compound 5 inhibited the activation of IFNβ promoter in Sendai virus infected cells.

A New Fungal Diterpene Induces VDAC1-dependent Apoptosis in Bax/Bak-deficient Cells

Background: VDAC1 functions in both cellular metabolism and mitochondria-mediated apoptosis. Results: New compounds were identified that induce apoptosis by promoting VDAC1 oligomerization and apoptosis in a Bak- and Bak-independent manner. Conclusion: Bax and Bak are dispensable for VDAC1-mediated apoptosis, revealing a novel mechanism of apoptosis involving VDAC1 oligomerization. Significance: In cancers with Bax/Bak down-regulated, VDAC1-induced apoptosis offers a novel approach for tumor therapies. The pro-apoptotic Bax and Bak proteins are considered central to apoptosis, yet apoptosis occurs in their absence. Here, we asked whether the mitochondrial protein VDAC1 mediates apoptosis independently of Bax/Bak. Upon screening a fungal secondary metabolite library for compounds inducing apoptosis in Bax/Bak-deficient mouse embryonic fibroblasts, we identified cyathin-R, a new cyathane diterpenoid compound able to activate apoptosis in the absence of Bax/Bak via promotion of the VDAC1 oligomerization that mediates cytochrome c release. Diphenylamine-2-carboxilic acid, an inhibitor of VDAC1 conductance and oligomerization, inhibited cyathin-R-induced VDAC1 oligomerization and apoptosis. Similarly, Bcl-2 overexpression conferred resistance to cyathin-R-induced apoptosis and VDAC1 oligomerization. Silencing of VDAC1 expression prevented cyathin-R-induced apoptosis. Finally, cyathin-R effectively attenuated tumor growth and induced apoptosis in Bax/Bak-deficient cells implanted into a xenograft mouse model. Hence, this study identified a new compound promoting VDAC1-dependent apoptosis as a potential therapeutic option for cancerous cells lacking or presenting inactivated Bax/Bak.

Versicoamides F–H, Prenylated Indole Alkaloids from Aspergillus tennesseensis

Three highly modified indole alkaloids, versicoamides F-H (1-3), together with seven known alkaloids (4-10) were isolated from the fungus Aspergillus tennesseensis. The structures of new compounds were determined by analysis of the NMR and MS spectroscopic data. The absolute configurations of 1 and 2 were assigned by single-crystal X-ray diffraction experiments. Compounds 1 and 2 showed weak antiproliferative activity against the H460 cell line. Compounds 1-3 represent a new class of natural product hybrids with new chemical skeletons.

Phaeolschidins A-E, five hispidin derivatives with antioxidant activity from the fruiting body of Phaeolus schweinitzii collected in the Tibetan Plateau.

Five new hispidin derivatives, phaeolschidins A-E (1-5), as well as two known natural products, pinillidine (6) and hispidin (7), were isolated from the fruiting bodies of Phaeolus schweinitzii collected in the Tibetan Plateau. The structures of the new compounds were elucidated by spectroscopic methods. Phaeolschidins A-D (1-4) are new bishispidins. Phaeolschidin E (5) is a new class of hispidin derivative in which one pyrrolidin-2-one moiety was linked to C-3 of hispidin. The antioxidant activity of 1-7 was evaluated using three methods: the DPPH scavenging assay, the total antioxidant capacity assay, and the lipid peroxidation assay. Hispidin showed the strongest antioxidant activity of all tested compounds. This is the first report of secondary metabolites from the fungus P. schweinitzii.

Cochlioquinone Derivatives with Apoptosis-Inducing Effects on HCT116 Colon Cancer Cells from the Phytopathogenic Fungus Bipolaris luttrellii L439

A new cochlioquinone derivative, cochlioquinone F (1), as well as three known compounds, anhydrocochlioquinone A (2), isocochlioquinone A (3), and isocochlioquinone C (4), were isolated from the PDB (potato dextrose broth) culture of the phytopathogenic fungus Bipolaris luttrellii. The structure of 1 was elucidated on the basis of NMR techniques. The apoptosis‐inducing effects of compounds 1–4 were evaluated against HCT116 cancer cells. Compound 2 exhibited the strongest activity in inducing apoptosis on HCT116 cells within the range of 10–30 μM. In addition, the caspase activation, the release of cytochrome c from mitochondria, and the downregulation of Bcl‐2 protein in HCT116 cells treated with compound 2 were detected.

Correction to Versicoamides F–H, Prenylated Indole Alkaloids from Aspergillus tennesseensis

of compounds Versicoamides F−H (1−3), notoamide O (7), notoamide Q (8), and dehydronotoamide E (9) are incorrect and should be Versicolamides F−H (1−3), notoamide Q (7), dehydronotoamide C (8), and 17-epi-notoamide Q (9), respectively. The reference to 17-epi-notoamide Q (9) (Nat. Chem. 2009, 1, 63−68) should be replaced with the reference shown below. The authors apologize to the scientific community for the inconvenience caused by these errors.

New Cyclohexadepsipeptides from an Entomogenous Fungus Fusarium proliferatum and Their Cytotoxicity and Autophagy-Inducing Activity

Five new cyclohexadepsipeptides termed as enniatins R – V (1 – 5) and seven known cyclohexadepsipeptides (6 – 12) were isolated from the solid culture of Fusarium proliferatum, a fungus isolated from the cadaver of an unidentified insect collected in Tibet. Their structures were elucidated by NMR and MS spectroscopic analysis. The X‐ray single‐crystal structure of 6 was reported for the first time. Enniatins R and S represented the first enniatins incorporating with an unusual 2,3‐dihydroxy‐isovaleric acid (Div) residue. The cytotoxicity and autophagy‐inducing activities of 1 – 12 were evaluated in vitro. Beauvenniatin F (11) exhibited strong cytotoxicity against K562/A (adriamycin‐resistant K562) with IC50 value of 3.78 μm, and also autophagy‐inducing activity at the concentration of 20 μm in GFP‐LC3 stable HeLa cells.