Immunosuppressive steroids quadrilisteroids A-C and derivatives from the terrestrial fungus Aspergillus quadrilineatus.

Seven undescribed compounds (1-7) along with six known compounds (8-13) were isolated from Eurotiaceae Aspergillus quadrilineatus. Their structures and absolute configurations were elucidated by NMR, HRESIMS, and ECD calculations. Quadrilisteroids A (1) and B (2) possessed an unprecedented 6/5/6/6/6/5 hexacyclic ring system in conjugation with a highly fused benzene ring, while quadrilisteroid C (3) featured a surprising 6/6/6/5/5-fused carbocyclic skeleton. Quadrilisteroid C (3) exhibited potent inhibitory activity against LPS-induced proliferation of B lymphocyte cells with an IC50 value of 1.03 µM. Compound 4, demonstrated inhibitory activity against Con A-induced proliferation of T lymphocyte cells with IC50 values of 6.42 µM.

Three new Furano-lactones from the endophytic fungus Aspergillus nidulans.

Three new furano-lactones, asperilactones A-C (1-3), and two known compounds silvaticol (4) and violaceic acid (5) were isolated from an ethanol extract of Aspergillus nidulans, a fungus isolated from the Annelida Whitmania pigra Whitman (Haemopidae). Their structures were elucidated by a combination of spectroscopy, ECD calculations, comparing optical rotation values, and single-crystal X-ray diffraction analyses. Asperilactone A (1) represented the first example of furano-lactone with an unusual 2-thia-6-oxabicyclo[3.3.0]octane ring system. Asperilactones A and B showed weak toxicity against the HL-60 and RKO.

Spectasterols, Aromatic Ergosterols with 6/6/6/5/5, 6/6/6/6, and 6/6/6/5 Ring Systems from Aspergillus spectabilis.

Spectasterols A-E (1-5), aromatic ergosterols with unique ring systems, were isolated from Aspergillus spectabilis. Compounds 1 and 2 possess a 6/6/6/5/5 ring system with an additional cyclopentene, while 3 and 4 have an uncommon 6/6/6/6 ring system generated by the D-ring expansion via 1,2-alkyl shifts. Compound 3 exhibited cytotoxic activity (IC50 6.9 µM) and induced cell cycle arrest and apoptosis in HL60 cells. Compound 3 was anti-inflammatory; it decreased COX-2 levels at the transcription and protein levels and inhibited the nuclear translocation of NF-κB p65.

Asperemestrins A-D, Emestrin Hybrid Polymers with Bridged Skeletons from the Endophytic Fungus Aspergillus nidulans.

Four emestrin hybrid polymers, asperemestrins A-D (1-4, respectively), were isolated from the fungus Aspergillus nidulans. Asperemestrins A-C are the first examples of emestrin-sterigmatocystin heterodimers bearing a 7/5/6/6/5/5/6/6/6 nonacyclic system with a 2,5-diazabicyclo[2.2.2]octane-3,6-dione core, while asperemestrin D features an unprecedented 2,15-dithia-17,19-diazabicyclo[14.2.2]icosa-4,8-diene-12,18,20-trione core skeleton. Their structures were determined by extensive spectroscopic data, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Asperemestrin B showed moderate cytotoxicity against cancer cell lines, including SU-DHL-2, HEPG2, and HL-60.

30-norlanostane triterpenoids and steroid derivatives from the endophytic fungus Aspergillus nidulans.

Two undescribed 30-norlanostane triterpenoids, named nidulanoids A and B, one ergostane-type steroid with an unusual double bond between C-17 and C-20 designated (17E,22E,24R)-3ß,5α-dihydroxyergosta-7,17,22-trien-6,16-dione, and one pregnane, (7Z,9Z,17Z)-,2α,3ß-dihydroxypregna-7,9,17 (20)-trien-18-al, along with six known steroids were isolated from the extract of the fungus Aspergillus nidulans. Among them, nidulanosides A and B represents the first example of naturally occurred 30-norlanostane triterpenoids featuring a C9 side-chain moiety at C-17 and a hemiacetal system formed between C-3 and C-19, as an intermediate between lanostane and the regular steriods; the structure of (17E,22E,24R)-3ß,5α-dihydroxyergosta-7,17,22-trien-6,16-dione possesses an untypical Δ17,20 double bond; meanwhile, (7Z,9Z,17Z)-,2α,3ß-dihydroxypregna-7,9,17 (20)-trien-18-al represents the first example of C-21 steroid with an aldehyde group at C-13. Their structures and absolute stereochemistry were elucidated based on spectroscopic data, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. (7Z,9Z,17Z)-,2α,3ß-dihydroxypregna-7,9,17 (20)-trien-18-al showed moderate inhibitory activities against rat brain cancer (PC12) cell lines, with IC50 value of 7.34 µM. This study enriches the diversified structures of triterpenoids and steroids analogues from A. nidulans and indicated (7Z,9Z,17Z)-,2α,3ß-dihydroxypregna-7,9,17(20)-trien-18-al to be a promising lead compound against PC12 cell lines.