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Fifteen secondary metabolites, including five new sesquiterpenoids (1 – 5), one new benzofuranoid (10), one new ophiobolin sesterterpenoid (11), and one new 3,5-dimethylorsellinic acid (DMOA)-based meroterpenoid (15), as well as seven known analogues (6 – 9 and 12 – 14), were isolated and characterized from fungus Aspergillus calidoustus , which was separated from the wetland soil collected at Dianchi Lake, Yunnan Province. Compound 5 featured an unusual dioxolane moiety, and compound 15 was a rare austin meroterpenoid analogue with the opened A ring, and also featured an undescribed oxygen bridge between C-3 and C-16 to construct an unexpected tetrahydrofuran ring. Their structures were established by widespread spectroscopic methods, single-crystal X-ray diffraction experiments, and ECD calculation. All the isolated drimane sesquiterpenoids were evaluated for the in vitro cytotoxicity against five tumor cell lines, including SW480 (colon cancer), IOMM-Lee (meningioma), HeLa (cervical cancer), FARAGE (diffuse large B-cell lymphoma), and SU-DHL-4 (diffuse large B-cell lymphoma). Compound 9 exhibited significant cytotoxicity against FARAGE and SU-DHL-4 tumor cell lines with IC 50 values of 5.54 and 9.78 μM, respectively. Further mechanism study showed that 9 could significantly promote apoptosis in FARAGE and SU-DHL-4 cell lines by interfering with mitochondrial function. [Display omitted] • Eight new metabolites were isolated from a soil-derived fungus Aspergillus calidoustus. • Their structures were established by widespread spectroscopic methods and single-crystal X-ray diffraction. • Compound 15 represented a rare austin analogue with the opened A ring, and also featured an undescribed oxygen bridge between C-3 and C-16 to construct an unexpected furan ring. • Compound 9 exhibited significant cytotoxicity against FARAGE and SU-DHL-4 tumor cell lines with IC 50 values of 5.54 and 9.78 μM, respectively. • Further mechanism study showed that compound 9 could significantly promote apoptosis in FARAGE and SU-DHL-4 cell lines by interfering with mitochondrial function. Fifteen secondary metabolites, including five new sesquiterpenoids (1 – 5), one new benzofuranoid (10), one new ophiobolin sesterterpenoid (11), and one new 3,5-dimethylorsellinic acid (DMOA)-based meroterpenoid (15), as well as seven known analogues (6 – 9 and 12 – 14), were isolated and characterized from fungus Aspergillus calidoustus , which was separated from the wetland soil collected at Dianchi Lake, Yunnan Province. Compound 5 featured an unusual dioxolane moiety, and compound 15 was a rare austin meroterpenoid analogue with the opened A ring, and also featured an undescribed oxygen bridge between C-3 and C-16 to construct an unexpected tetrahydrofuran ring. Their structures were established by widespread spectroscopic methods, single-crystal X-ray diffraction experiments, and ECD calculation. All the isolated drimane sesquiterpenoids were evaluated for the in vitro cytotoxicity against five tumor cell lines, including SW480 (colon cancer), IOMM-Lee (meningioma), HeLa (cervical cancer), FARAGE (diffuse large B-cell lymphoma), and SU-DHL-4 (diffuse large B-cell lymphoma). Compound 9 exhibited significant cytotoxicity against FARAGE and SU-DHL-4 tumor cell lines with IC 50 values of 5.54 and 9.78 μM, respectively. Further mechanism study showed that 9 could significantly promote apoptosis in FARAGE and SU-DHL-4 cell lines by interfering with mitochondrial function. [ABSTRACT FROM AUTHOR]

Large-scale culture is a complementary and practical method for genome mining and OSMAC approaches to discover novel natural products through accumulation and reprocessing effects. By employing a large-scale culture approach, twelve 3,5-dimethylorsellinic acid (DMOA)-based meroterpenoids, including five undescribed compounds, namely asperanstinoids A–E, were obtained from fungus Aspergillus calidoustus , which was isolated from the wetland soil collected at Dianchi Lake, Yunnan Province. The structures and absolute configurations of asperanstinoids A–E were determined by various spectroscopic analyses, including NMR spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS), single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations, and the absolute configurations of three known compounds, dehydroaustinol, austinol, and austin, were confirmed via single-crystal X-ray diffraction for the first time. Notably, asperanstinoid A represents the second example of a DMOA-based meroterpenoid featuring a unique 6/5/6/6/6/5-fused hexacyclic skeleton with a rare "1,13-epoxy" moiety. The cytotoxicity assay of all these isolates revealed that asperanstinoid D, dehydroaustinol, and austin displayed considerable cytotoxicity against the HL-60 and SU-DHL-4 tumor cell lines with IC 50 values ranging from 15.7 to 27.8 μ M. [Display omitted] • Five undescribed meroterpenoids were characterized from Aspergillus calidoustus. • Their structures were defined by NMR analyses, ECD calculations, and X-ray crystallography. • Asperanstinoid A possesses a rare 6/5/6/6/6/5-fused ring system with a "1,13-epoxy" moiety. • Asperanstinoid D, dehydroaustinol, and austin displayed considerable cytotoxicity. [ABSTRACT FROM AUTHOR]