Asperustins A-J: Austocystins with Immunosuppressive and Cytotoxic Activities from Aspergillus ustus NRRL 5856.

Ten new (1-10) and nine known (11-19) austocystins, along with four known anthraquinones (20-23), were isolated from the culture of Aspergillus ustus NRRL 5856 by bioactivity-guided fractionation. The structures of the new compounds were elucidated by spectroscopic data analysis, X-ray crystallographic study, the modified Mosher's method, [Rh2(OCOCF3)4]-induced ECD spectral analysis, and comparison of the experimental ECD spectra with those of the similar analogues. Compounds 1-8 represent the first examples of austocystins with a C-4' oxygenated substitution. The absolute configuration of 1″-hydroxy austocystin D (11) was determined by single-crystal X-ray diffraction and consideration of its biosynthetic origin. Compounds 5, 9, and 11 exhibited significant inhibitory effects against the proliferation of ConA-induced T cells with IC50 values of 1.1, 1.0, and 0.93 µM, respectively. Furthermore, these compounds suppressed the expression of IL-6 in a dose-dependent manner. Compounds 10-12 and 14 showed pronounced cytotoxicities against MCF-7 with IC50 values of 3.9, 1.3, 0.46, and 2.3 µM, respectively.

Diaporaustalides A-L, Austalide Meroterpenoids from a Plant Endophytic Diaporthe sp.

Twelve new austalide meroterpenoids (1-12) were isolated from the endophytic fungus Diaporthe sp. XC1211. Their structures were elucidated by extensive spectroscopic analysis. The absolute configurations of compounds 1, 3, 4, and 6 were established by single-crystal X-ray diffraction, whereas those for the others were established by experimental electronic circular dichroism (ECD) data analysis. Compounds 1-12 represent a rare class of austalides with a 24α-CH3. Compounds 2 and 5 demonstrated potent proliferation inhibitory effects against LPS-induced B cells with IC50 values of 6.7 (SI = 3.6) and 3.8 (SI > 13) µM, respectively. Compounds 2 and 5 decreased the secretion of IL-6 in LPS-induced B cells in a dose-dependent manner.

Peniandranoids A-E: Meroterpenoids with Antiviral and Immunosuppressive Activity from a Penicillium sp.

Peniandranoids A-E (1-5), five new meroterpenoids, together with three known analogues (6-8), were isolated from the fermentation of a soil-derived fungus, Penicillium sp.sb62. Their structures including absolute configurations were determined by extensive spectroscopic analysis, and the absolute configurations of compounds 1 and 5 were further elucidated by single-crystal X-ray diffraction. Peniandranoids A-E belong to a rare class of andrastin-type meroterpenoids incorporating an extra polyketide unit (a C10 polyketide unit for 1 and 2, a C9 polyketide unit for 3 and 4, and a furancarboxylic acid unit for 5). Compounds 1 and 6 exhibited favorable inhibitory activities against influenza virus A (H1N1) with EC50 values of 19 and 14 µg/mL, respectively. Compounds 3-8 exhibited potent immunosuppressive activities against concanavalin A-induced T cell proliferation with EC50 values ranging from 4.3 to 27 µM and lipopolysaccharide-induced B cell proliferation with EC50 values ranging from 7.5 to 23 µM, respectively.

Aspersteroids A-C, Three Rearranged Ergostane-type Steroids from Aspergillus ustus NRRL 275.

Aspersteroid A (1), a highly rearranged 1(10 → 6)-abeo-18,22-cyclosterol, together with two new 18,22-cyclosterols (2 and 3), was isolated from the culture extract of Aspergillus ustus NRRL 275. Their structures were determined by spectroscopic analysis, X-ray diffraction, modified Mosher's method, and Rh2(OCOCF3)4-induced electronic circular dichroism experiments. Compound 1 represents a new carbon skeleton with an uncommon 6/6/6/5/5 ring system, which is presumably biosynthesized from A-ring scission, double 1,2-shifts, and C-18/C-22 cyclization. Compound 1 exhibited potent immunosuppressive and antimicrobial activities.

Antimicrobial Furancarboxylic Acids from a Penicillium sp.

Ten novel (1, 2, 3a, 3b, 4a, 4b, 5a, 5b, 6a, and 6b) furancarboxylic acids including four pairs of epimers (3a, 3b; 4a, 4b; 5a, 5b; 6a, 6b), together with seven known analogues (7a, 7b, 8a, 8b, 9a, 9b, and 10), were isolated from the fermentation of the soil-derived fungus Penicillium sp. sb62. Their structures were established on the basis of spectroscopic data analysis, and the absolute configurations were determined by time-dependent density functional theory electronic circular dichroism calculations, comparison of the specific optical rotation values, and modified Mosher's method. Compounds 1-4 represent the first class of natural furancarboxylic acids featuring a thiophene moiety. Compounds 1-7 showed antimicrobial inhibitory activities against Escherichia coli, Staphylococcus aureus, and Candida albicans with MIC values ranging from 0.9 to 7.0 µg/mL, from 1.7 to 3.5 µg/mL, and from 3.3 to 7.0 µg/mL, respectively.

Pchaeglobolactone A, Spiropchaeglobosin A, and Pchaeglobosals A and B: Four Rearranged Cytochalasans from Chaetomium globosum P2-2-2.

Four novel rearranged cytochalasans (1-4) were isolated from an endophytic fungus Chaetomium globosum P2-2-2. Pchaeglobolactone A (1) possessed an unprecedented 13-aza-21-oxa-tetracyclo-[10.6.1.217,19.015,19]henicosane core. Spiropchaeglobosin A (2) was the first example of cytochalasans featuring a novel spiro[5.10]hexadecane unit. Pchaeglobosals A (3) and B (4) featured a unique 5/5/13 fused tricyclic ring system. Compounds 1-4 were tested for their antiproliferative, apoptosis, cell cycle arrest, and TRAIL-resistance-overcoming activities on cancer cell lines.

Resorcylic Acid Lactones from an Ilyonectria sp.

Twelve new resorcylic acid lactones (RALs) including three new 16-membered RALs (1a, 1b and 2), eight new 14-membered RALs (3-10), and one new 12-membered RAL (11), along with five known 14-membered RALs (12-16), were identified from the fermentation of the soil-derived fungus Ilyonectria sp. sb65. Their structures were established by detailed analyses of 1D and 2D NMR, HRESIMS, and X-ray diffraction crystallography. All new compounds were evaluated for their cytotoxic effects against three human cancer cell lines, along with their potential as TRAIL sensitizers in TRAIL-resistant A549 human lung adenocarcinoma cells and their in vitro immunosuppressive effects against ConA-induced T-cell and LPS-induced B-cell proliferation.