Tetracenomycin X Exerts Antitumour Activity in Lung Cancer Cells through the Downregulation of Cyclin D1

Tetracenomycin X (Tcm X) has been reported to have antitumour activity in various cancers, but there have not been any studies on its activity with respect to lung cancer to date. Therefore, this study aims to investigate the anti-lung cancer activity of Tcm X. In this study, we found that tetracenomycin X showed antitumour activity in vivo and selectively inhibited the proliferation of lung cancer cells without influencing lung fibroblasts. In addition, apoptosis and autophagy did not contribute to the antitumour activity. Tetracenomycin X exerts antitumour activity through cell cycle arrest induced by the downregulation of cyclin D1. To explore the specific mechanism, we found that tetracenomycin X directly induced cyclin D1 proteasomal degradation and indirectly downregulated cyclin D1 via the activation of p38 and c-JUN proteins. All these findings were explored for the first time, which indicated that tetracenomycin X may be a powerful antimitotic class of anticancer drug candidates for the treatment of lung cancer in the future

Cadinane sesquiterpenes from the leaves of Eupatorium adenophorum

Four new cadinane sesquiterpenes (1-4), including a dimeric cadinane derivative (2) and a peroxide cadinane analogue (3), have been isolated from the leaves of Eupatorium adenophorum. Their Structures including absolute configurations were determined oil the basis of spectroscopic data interpretation and single-crystal X-ray crystallography. Compound 4 showed in vitro cytotoxicity against the HCT-8, Bel-7402, and A2780 cancer cell lines

Seco-Tetracenomycins from the Marine-Derived Actinomycete Saccharothrix sp. 10-10

Six new tetracenomycin congeners, saccharothrixones E–I (1–5) and 13-de-O-methyltetracenomycin X (6), were isolated from the rare marine-derived actinomycete Saccharothrix sp. 10-10. Their structures were elucidated by spectroscopic analysis and time-dependent density functional theory (TDDFT)-electronic circular dichroism (ECD) calculations. Saccharothrixones G (3) and H (4) are the first examples of tetracenomycins featuring a novel ring-A-cleaved chromophore. Saccharothrixone I (5) was determined to be a seco-tetracenomycin derivative with ring-B cleavage. The new structural characteristics, highlighted by different oxidations at C-5 and cleavages in rings A and B, enrich the structural diversity of tetracenomycins and provide evidence for tetracenomycin biosynthesis. Analysis of the structure–activity relationship of these compounds confirmed the importance of the planarity of the naphthacenequinone chromophore and the methylation of the polar carboxy groups for tetracenomycin cytotoxicity

Zelkovamycins B–E, cyclic octapeptides containing rare amino acid residues from an endophytic <i>Kitasatospora </i>sp

Four unusual cyclopeptides, zelkovamycins B–E (1–4), were isolated from an endophytic Kitasatospora sp. Zelkovamycin B was featured by an unprecedented 3-methyl-5-hydroxypyrrolidine-2,4-dione ring system linked to the cyclopeptide skeleton. Their structures and full configurations were established by spectroscopic analysis, Marfey’s method, and NMR calculations. A plausible biosynthetic pathway for zelkovamycins was proposed based on gene cluster analysis. Zelkovamycin E displayed potent inhibitory activity against H1N1 influenza A virus

Dammarane Glycosides from the Root of <i>Machilus yaoshansis</i>

Nine new dammarane triterpene glycosides (<b>1</b>–<b>3</b> and <b>8</b>–<b>13</b>) and 12 known analogues have been isolated from an ethanol extract of the roots of <i>Machilus yaoshansis</i>. Compounds <b>1</b>–<b>7</b> have an uncommon 20,23-dihydroxydammar-24-en-21-oic acid-21,23-lactone moiety that was previously reported in compounds isolated from <i>Gynostemma pentaphyllum</i>. The configurations of the lactone moieties in <b>1</b>–<b>3</b> were determined by comparison of the experimental ECD spectra of <b>1</b>–<b>3</b> and the hydrolysates, <b>1a</b> and <b>1b</b>, with the corresponding calculated ECD spectra. On the basis of NMR and ECD data analysis of <b>1</b>–<b>7</b>, the previously reported C-20 and C-23 configurations of <b>4</b>–<b>7</b> and related derivatives from <i>Gynostemma pentaphyllum</i> were revised. In addition, the application of NMR data and Cotton effects to the determination of the relative and absolute configurations of the γ-lactone moiety in 3β,20,23-trihydroxydammar-24-en-21-oic acid-21,23-lactone derivatives is discussed

Antimicrobial and Anti-inflammatory Cyclic Tetrapeptides from the Co-cultures of Two Marine-Derived Fungi

Violaceotides B–E (1–4), four new cyclic tetrapeptides, along with seven known compounds, were identified from the sponge-associated Aspergillus insulicola IMB18-072 co-cultivated with the marine-derived Alternaria angustiovoidea IMB20-805. Their structures were elucidated by extensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR, and MS/MS data. The absolute configurations were determined by the advanced Marfey’s method. Compounds 2, 3, and violaceotide A (5) displayed selective antimicrobial activities against the aquatic pathogenic bacteria Edwardsiella tarda and E. ictaluri. In addition, compounds 1–5 showed inhibitory activities against the LPS-induced expression of the inflammatory mediator IL-6 in RAW264.7 cells at a concentration of 10 μM

Antimicrobial and Anti-inflammatory Cyclic Tetrapeptides from the Co-cultures of Two Marine-Derived Fungi

Violaceotides B–E (1–4), four new cyclic tetrapeptides, along with seven known compounds, were identified from the sponge-associated Aspergillus insulicola IMB18-072 co-cultivated with the marine-derived Alternaria angustiovoidea IMB20-805. Their structures were elucidated by extensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR, and MS/MS data. The absolute configurations were determined by the advanced Marfey’s method. Compounds 2, 3, and violaceotide A (5) displayed selective antimicrobial activities against the aquatic pathogenic bacteria Edwardsiella tarda and E. ictaluri. In addition, compounds 1–5 showed inhibitory activities against the LPS-induced expression of the inflammatory mediator IL-6 in RAW264.7 cells at a concentration of 10 μM

4862F, a New Inhibitor of HIV-1 Protease, from the Culture of Streptomyces I03A-04862

We have isolated an extraordinary pentapeptide, called 4862F, from the culture broth of Streptomyces albosporus I03A-04862 by Diaion HP-20 macroporous adsorbent resin column, ODS-A and Sephadex LH-20 chromatography, followed by preparative HPLC. This peptide shows inhibitory activity against HIV-1 protease. The structure was elucidated by spectroscopic approaches, including ESI-MS and various NMR methods. Absolute configuration of the amino acid residues in 4862F was defined using Marfey’s method, and the structure was identified as N,N,N-(trimethylated)-Tyr-L-Leu-L-Val-L-Leu-(dehydrated)-His. The peptide 4862F displays inhibitory activity against HIV-1 protease, with IC50 values of 15.26 nM, using a fluorescence-based assay

Saccharothrixones A–D, Tetracenomycin-Type Polyketides from the Marine-Derived Actinomycete <i>Saccharothrix</i> sp. 10-10

Saccharothrixones A–C (<b>1</b>–<b>3</b>), three new aromatic polyketide <i>seco</i>-tetracenomycins, and saccharothrixone D (<b>4</b>), a new tetracenomycin analogue possessing opposite configurations at all of the stereogenic centers, were isolated from the marine-derived actinomycete <i>Saccharothrix</i> sp. 10-10. Compounds <b>1</b>–<b>3</b> represent the first examples of <i>seco</i>-tetracenomycins where the quinone ring B is cleaved and re-formed into a furanone ring. Their structures were elucidated by spectroscopic analyses and ECD calculations. The absolute configuration of <b>4</b> was confirmed by single-crystal X-ray diffraction analysis. Saccharothrixone D (<b>4</b>) showed <i>in</i> <i>vitro</i> cytotoxic activity against the HepG2 cancer cell line with an IC₅₀ value of 7.5 μM