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Pulmonary fibrosis is a scarring disease of lung tissue, which seriously threatens human health. Treatment options are currently limited, and effective strategies are still lacking. In the present study, 25 compounds were isolated from the deep-sea fungus Trichoderma sp. MCCC 3A01244. Among them, two β-carboline alkaloids, trichocarbolines A (1) and C (4) are new compounds. The chemical structures of these compounds were elucidated based on their HRESIMS, 1D and 2D NMR spectra, optical rotation calculation, and comparisons with data reported in the literature. Trichocarboline B [(+)- and (–)-enantiomers] had previously been synthesized, and this is its first report as a natural product. Their anti-pulmonary fibrosis (PF) activity and cytotoxicity were investigated. Compounds 1, 11, and 13 strongly inhibited TGF-β1-induced total collagen accumulation and showed low cytotoxicity against the HFL1 cell line. Further studies revealed compound 1 inhibited extracellular matrix (ECM) deposition by downregulating the expression of protein fibronectin (FN), proliferating cell nuclear antigen (PCNA), and α-smooth muscle actin (α-SMA). Mechanistic study revealed that compound 1 decreased pulmonary fibrosis by inhibiting the TGF-β/Smad signaling pathway. As a newly identified β-carboline alkaloid, compound 1 may be used as a lead compound for developing more efficient anti-pulmonary fibrosis agents.

A new compound, exophilone (1), together with nine known compounds (2–10), were isolated from a deep-sea-derived fungus, Exophiala oligosperma. Their chemical structures, including the absolute configuration of 1, were elucidated using nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionization mass spectroscopy (HRESIMS), and electronic circular dichroism (ECD) calculation. Compounds were preliminarily screened for their ability to inhibit collagen accumulation. Compounds 1, 4, and 7 showed weaker inhibition of TGF-β1-induced total collagen accumulation in compared with pirfenidone (73.14% inhibition rate). However, pirfenidone exhibited cytotoxicity (77.57% survival rate), while compounds 1, 4, and 7 showed low cytotoxicity against the HFL1 cell line. Particularly, exophilone (1) showed moderate collagen deposition inhibition effect (60.44% inhibition rate) and low toxicity in HFL1 cells (98.14% survival rate) at a concentration of 10 μM. A molecular docking study suggests that exophilone (1) binds to both TGF-β1 and its receptor through hydrogen bonding interactions. Thus, exophilone (1) was identified as a promising anti-pulmonary fibrosis agent. It has the potential to be developed as a drug candidate for pulmonary fibrosis.

By the method of 1H NMR prescreening and tracing the diagnostic signals, 6-methylpyridinone derivatives, (8R,9S)-dihydroisoflavipucine (1), (8S,9S)-dihydroisoflavipucine (2), 3-(1-hydroxy-4-methyl-2-oxopentylidene)-6-methylpyridine-2,4(1H,3H)-dione (3), 4-hydroxy-3-(2-hydroxy-4-methylpentanoyl)-6-methylpyridin-2(1H)-one (4), 4-hydroxy-3-[(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)methyl]-6-methylpyridin-2(1H)-one (5) and a known 6-methylpyranone derivative 3,3′-methylenebis(4-hydroxy-6-methyl-2H-pyran-2-one) (6) were isolated from the marine fungus Leptosphaerulina sp., which was collected from the starfish Acanthaster planci from the South China Sea. Compounds 2 and 3 are new compounds. Their structures were elucidated on the basis of MS, 1D and 2D NMR, and X-ray single crystal diffraction data. The absolute configurations of compounds 1 and 2 were determined by analysis on the experimental circular-dichroism spectra.

Three new compounds, monarubins A−C (1, 6 and 13), together with ten known compounds, including four alkaloids (2−5), two isocoumarins (7 and 8) and four polyketides (9−12), were isolated from marine shellfish-associated fungus Monascus ruber BB5. The structures were determined on the basis of the 1D and 2D NMR, MS, UV and IR data. The absolute configurations of compounds 3, 6 and 13 were determined by ECD calculations. The NMR data of compounds deoxyhydroxyaspergillic acid (3) and 2-hydroxy-6-(1-hydroxy-1-methylpropyl)-3-sec-buthylpyrazine (4) were first reported. All of the isolated compounds were evaluated for their cytotoxic activities against human nasopharyngeal carcinoma cell lines CNE1, CNE2, SUNE1 and HONE1 and hepatocellular carcinoma cell lines QGY7701 and HepG2. Monarubin B (6) displayed potent cytotoxicities against the cancer cell lines HepG2 and QGY7701 with IC50 values of 1.72 and 0.71 μΜ, respectively; lunatinin (7) showed moderate cytotoxic activities against the cancer cell lines HepG2, QGY7701 and SUNE1 with the IC50 values of 9.60, 7.12 and 28.12 μΜ, respectively.

The production of fungal metabolites can be remarkably influenced by various cultivation parameters. To explore the biosynthetic potentials of the marine fungus, Neosartorya pseudofischeri, which was isolated from the inner tissue of starfish Acanthaster planci, glycerol-peptone-yeast extract (GlyPY) and glucose-peptone-yeast extract (GluPY) media were used to culture this fungus. When cultured in GlyPY medium, this fungus produced two novel diketopiperazines, neosartins A and B (1 and 2), together with six biogenetically-related known diketopiperazines,1,2,3,4-tetrahydro-2, 3-dimethyl-1,4-dioxopyrazino[1,2-a]indole (3), 1,2,3,4-tetrahydro-2-methyl-3-methylen e-1,4-dioxopyrazino[1,2-a]indole (4), 1,2,3,4-tetrahydro-2-methyl-1,3,4-trioxopyrazino[1,2-a] indole (5), 6-acetylbis(methylthio)gliotoxin (10), bisdethiobis(methylthio)gliotoxin (11), didehydrobisdethiobis(methylthio)gliotoxin (12) and N-methyl-1H-indole-2-carboxamide (6). However, a novel tetracyclic-fused alkaloid, neosartin C (14), a meroterpenoid, pyripyropene A (15), gliotoxin (7) and five known gliotoxin analogues, acetylgliotoxin (8), reduced gliotoxin (9), 6-acetylbis(methylthio)gliotoxin (10), bisdethiobis(methylthio) gliotoxin (11) and bis-N-norgliovictin (13), were obtained when grown in glucose-containing medium (GluPY medium). This is the first report of compounds 3, 4, 6, 9, 10 and 12 as naturally occurring. Their structures were determined mainly by MS, 1D and 2D NMR data. The possible biosynthetic pathways of gliotoxin-related analogues and neosartin C were proposed. The antibacterial activity of compounds 2–14 and the cytotoxic activity of compounds 4, 5 and 7–13 were evaluated. Their structure-activity relationships are also preliminarily discussed.

Two novel isobenzofuranone derivatives, pseudaboydins A (1) and B (2), along with five known compounds, including (R)-2-(2-hydroxypropan-2-yl)-2,3-dihydro-5-hydroxybenzofuran (3), (R)-2-(2-hydroxypropan-2-yl)-2,3-dihydro-5-methoxybenzofuran (4), 3,3′-dihydroxy-5,5′-dimethyldiphenyl ether (5), 3-(3-methoxy-5-methylphenoxy)-5-methylphenol (6) and (−)-regiolone (7), were isolated from the culture broth of the marine fungus, Pseudallescheria boydii, associated with the starfish, Acanthaster planci. Their structures were elucidated primarily based on NMR and MS data. The absolute configurations of 1–4 were determined by CD spectroscopy and single-crystal X-ray diffraction studies. The cytotoxic and antibacterial activities of 1–4 were evaluated. Pseudaboydin A (1) showed moderate cytotoxic activity against human nasopharyngeal carcinoma cell line HONE1, human nasopharyngeal carcinoma cell line SUNE1 and human glandular lung cancer cell line GLC82 with IC50 values of 37.1, 46.5 and 87.2 μM, respectively.

Bioassay-guided fractionation of an ethanol extract of the pericarps of Garcinia mangostana led to the isolation of two new prenylated xanthones, named 1,3,7-trihydroxy-2-(3-methyl-2-butenyl)-8-(3-hydroxy-3-methylbutyl)-xanthone (1) and 1,3,8-trihydroxy-2-(3-methyl-2-butenyl)-4-(3-hydroxy-3-methylbutanoyl)-xanthone (2), together with the five known compounds garcinones C (3) and D (4), gartanin (5), xanthone I (6), and γ-mangostin (7). Their structures were elucidated primarily based on MS and NMR data. Compounds 1–7 showed significant cytotoxic activities against various human cancer cell lines.

Chondrostereum sp., a marine fungus isolated from a soft coral Sarcophyton tortuosum, can yield hirsutane framework sesquiterpenoids. However, the metabolites profiles vary dramatically with the composition change of the culture media. This fungus was cultured in a liquid medium containing glycerol as the carbon source, and two new metabolites, chondrosterins I and J (1 and 2), were obtained. Their structures were elucidated primarily based on MS, NMR and X-ray single-crystal diffraction data. By comparison with the known hirsutane sesquiterpenoids, chondrosterins I and J have unique structural features, including a methyl was migrated from C-2 to C-6, and the methyl at C-3 was carboxylated. Compound 2 exhibited potent cytotoxic activities against the cancer cell lines CNE-1 and CNE-2 with the IC50 values of 1.32 and 0.56 μM.

The composition of the culture medium has great influence on the metabolite production of the marine fungus Pseudallescheria boydii F44-1. By adding amino acids to GPY culture medium, two new bisindole alkaloids, pseudboindoles A and B (1 and 2), together with 11 known indole alkaloids were isolated from the culture broth. Their structures were elucidated by comprehensive analysis of the NMR, MS, IR, and UV spectra. The 3,3′-cyclohexylidenebis(1H-indole) (3) showed cytotoxic activity against various cancer cell lines.

The marine fungus Chondrostereum sp. was collected from a soft coral of the species Sarcophyton tortuosum from the South China Sea. Three new compounds, chondrosterins F–H (1, 4 and 5), together with three known compounds, incarnal (2), arthrosporone (3), and (2E)-decene-4,6,8-triyn-1-ol (6), were isolated. Their structures were elucidated primarily based on NMR and MS data. Incarnal (2) exhibited potent cytotoxic activity against various cancer cell lines.

The marine fungus Chondrostereum sp. was collected from a soft coral Sarcophyton tortuosum from the South China Sea. This fungus was cultured in potato dextrose broth medium and the culture broth was extracted with EtOAc. Five new triquinane-type sesquiterpenoids, chondrosterins A–E (1–5), and the known sesquiterpenoid hirsutanol C (6), were isolated. The structures were elucidated mainly on the basis of NMR, MS, and X-ray single-crystal diffraction data. Chondrosterin A (1) showed significant cytotoxic activities against cancer lines A549, CNE2, and LoVo with IC50 values of 2.45, 4.95, and 5.47 μM, respectively.

Hirsutanol A is a novel sesquiterpene compound purified from the marine fungus Chondrostereum sp in the coral Sarcophyton tortuosum. Our previous studies had demonstrated that hirsutanol A exerted potent cytotoxic effect in many kinds of cancer cell lines. Here, the anticancer molecular mechanisms of hirsutanol A were investigated in breast cancer MCF-7 cells. The results showed that hirsutanol A could inhibit cell proliferation, elevate reactive oxygen species (ROS) level, and induce apoptosis and autophagy. Co-treatment with the potent antioxidant agent N-acetyl-l-cysteine could effectively reverse the effect of enhanced ROS production, which in turn, reduces growth inhibition, apoptosis, and autophagy mediated by hirsutanol A. In addition, blocking autophagy by bafilomycin A1 or Atg7-siRNA could synergistically enhance the antiproliferative effect and apoptosis induced by hirsutanol A. These data suggested that hirsutanol A could induce apoptosis and autophagy via accumulation of ROS and co-treatment with an autophagy inhibitor could sensitize MCF-7 cells to hirsutanol A. Keywords:: hirsutanol A, apoptosis, autophagy, reactive oxygen species (ROS), breast cancer

Linear triquinane sesquiterpenoids represent an important class of natural products. Most of these compounds were isolated from fungi, sponges, and soft corals, and many of them displayed a wide range of biological activities. On account of their structural diversity and complexity, linear triquinane sesquiterpenoids present new challenges for chemical structure identification and total synthesis. 118 linear triquinane sesquiterpenoids were classified into 8 types, named types I–VIII, based on the carbon skeleton and the position of carbon substituents. Their isolation, structure elucidations, biological activities, and chemical synthesis were reviewed. This paper cited 102 articles from 1947 to 2018.

In our continuous chemical investigation on the marine-derived fungus Dichotomomyces cejpii F31-1, two new polyketides dichocetides B-C (1, 2), two new alkaloids dichotomocejs E-F (3, 4), and three known fumiquinozalines: scequinadoline A (5), quinadoline A (6), and scequinadoline E (7) were discovered from the culture broth and the mycelium in the culture medium, by the addition of l-tryptophan and l-phenylalanine. Their chemical structures were established by one dimensional (1D), two dimensional (2D) nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HR-MS) data. Among them, scequinadoline A (5) exhibited significant inhibitory activity against dengue virus serotype 2 production by standard plaque assay, equivalent to the positive control andrographlide. Scequinadoline A (5) possesses the potential for further development as a dengue virus inhibitor.

By adding l-tryptophan and l-phenylalanine to GPY medium, twenty-eight compounds, including amides, polyketides, a sesquiterpenoid, a diterpenoid, a meroterpenoid, diketopiperazines, β-carbolines, fumiquinazolines, and indole alkaloids, were discovered from the marine-derived fungus Dichotomomyces cejpii F31-1, demonstrating the tremendous biosynthetic potential of this fungal strain. Among these compounds, four amides dichotomocejs A–D (1–4), one polyketide dichocetide A (5), and two diketopiperazines dichocerazines A–B (15 and 16) are new. The structures of these new compounds were determined by interpreting detailed spectroscopic data as well as calculating optical rotation values and ECD spectra. Obviously, Dichotomomyces cejpii can effectively use an amino acid-directed strategy to enhance the production of nitrogen-containing compounds. Dichotomocej A (1) displayed moderate cytotoxicity against the human rhabdomyosarcoma cell line RD with an IC50 value of 39.1 µM, and pityriacitrin (22) showed moderate cytotoxicity against the human colon carcinoma cell line HCT116 with an IC50 value of 35.1 µM.

Bioassay-guided isolation of the secondary metabolites from the fungus Dichotomomyces sp. L-8 associated with the soft coral Lobophytum crassum led to the discovery of two new compounds, dichotones A and B (1 and 2), together with four known compounds including dichotocejpin C (3), bis-N-norgliovictin (4), bassiatin (5) and (3R,6R)-bassiatin (6). The structures of these compounds were determined by 1D, 2D NMR and mass spectrometry. (3R,6R)-bassiatin (6) displayed significant cytotoxic activities against the human breast cancer cell line MDA-MB-435 and the human lung cancer cell line Calu3 with IC50 values of 7.34 ± 0.20 and 14.54 ± 0.01 μM, respectively, while bassiatin (5), the diastereomer of compound 6, was not cytotoxic.

By the method of 1H NMR prescreening and tracing the diagnostic proton signals of the methyl groups, three additional new triquinane-type sesquiterpenoids—chondrosterins K–M (1–3) and the known sesquiterpenoid anhydroarthrosporone (4)—were isolated from the marine fungus Chondrostereum sp. Their structures were elucidated on the basis of MS, 1D, and 2D NMR data. Chondrosterin K is a rare hirsutane sesquiterpenoid, in which a methyl group was migrated from C-2 to C-6 and has a double bond between C-2 and C-3. Compounds 1–3 showed significant cytotoxicities against various cancer cell lines in vitro.

Two additional new compounds, pseudellone D (1) and (5S,6S)-dihydroxylasiodiplodin (3), along with the two known compounds lasiodipline F (2), (5S)-hydroxylasiodiplodin (4) were isolated from the marine-derived fungus Pseudallescheria ellipsoidea F42-3 associated with the soft coral Lobophytum crassum. Their structures, including absolute configurations, were elucidated on the basis of the corresponding spectroscopic data and electronic circular dichroism (ECD) spectra.

The marine fungus Neosartorya pseudofischeri was isolated from Acanthaster planci from the South China Sea. In a preliminary bioactivity screening, the crude methanol extract of the fungal mycelia showed significant inhibitory activity against the Sf9 cell line from the fall armyworm Spodoptera frugiperda. Five novel compounds, including 5-olefin phenylpyropene A (1), 13-dehydroxylpyripyropene A (4), deacetylsesquiterpene (7), 5-formyl-6-hydroxy-8-isopropyl-2- naphthoic acid (9) and 6,8-dihydroxy-3-((1E,3E)-penta-1,3-dien-1-yl)isochroman-1-one (10), together with eleven known compounds, phenylpyropene A (2) and C (3), pyripyropene A (5), 7-deacetylpyripyropene A (6), (1S,2R,4aR,5R,8R,8aR)-1,8a-dihydroxy-2-acetoxy-3,8-dimethyl-5- (prop-1-en-2-yl)-1,2,4a, 5,6,7,8,8a-octahydronaphthalene (8), isochaetominine C (11), trichodermamide A (12), indolyl-3-acetic acid methyl ester (13), 1-acetyl-β-carboline (14), 1,2,3,4-tetrahydro-6-hydroxyl-2-methyl-l,3,4-trioxopyrazino[l,2-a]-indole (15) and fumiquinazoline F (16), were obtained. The structures of these compounds were determined mainly by MS and NMR data. The absolute configuration of 9 was assigned by the single-crystal X-ray diffraction studies. Compounds 1–11 and 15 showed significant cytotoxicity against the Sf9 cells from S. frugiperda.

The title compound [systematic name: 5,6,7-trimethoxy-2-(7-methoxy-1,3-dihydro-2-benzofuran-5-yl)-4H-chromen-4-one monohydrate], C20H18O8·H2O, was isolated from the popular Chinese medicinal plant Entada phaseoloides. In the crystal, inversion-related molecules are joined by pairs of weak C—H...O hydrogen bonds. The dimers are further interconnected by a bridging water molecule via weak C—H...Owater and pairs of (O—H)water...O hydrogen bonds into a linear tape running parallel to the b axis.