Marcanine G, a new cytotoxic 1-azaanthraquinone from the stem bark of <i>Goniothalamus marcanii</i> Craib

<p>The ethanolic extract from the stem bark of <i>Goniothalamus marcanii</i> Craib was shown in preliminary brine shrimp lethality data having good cytotoxic activity. Further bioassay guided isolation was done by means of solvent partition, chromatography and precipitation to provide four isolated compounds: a novel compound <b>1</b> with the core structure of 1-azaanthraquinone moiety referred as marcanine G; as well as compounds <b>2–4</b> with known aristolactam structures namely, piperolactam C, cepharanone B and taliscanine. These compounds were characterised by spectroscopic techniques. The assessment of cytotoxicity was established on an SRB assay using doxorubicin as a positive control. Marcanine G (<b>1</b>) was considered the most active compound indicating the IC₅₀ values of 14.87 and 15.18 μM against human lung cancer cells (A549) and human breast cancer cells (MCF7), respectively. However, <b>2</b> showed mild activity with the IC₅₀ values of 83.72 and 82.32 μM against A549 and MCF7 cells, respectively.</p

A new isomaneonene derivative from the red alga <i>Laurencia</i> cf. <i>mariannensis</i>

Determining the structures of new natural products from marine species not only enriches our understanding of the diverse chemistry of these species, but can also lead to the discovery of compounds with novel and/or important biological activities. Herein, we describe the isolation of isomaneonene C (1), a new halogenated C15 acetogenin, and three known compounds, α-snyderol (2), cis-maneonene D (3), and isomaneonene B (4), from the organic extract obtained from the red alga Laurencia cf. mariannensis collected from Iheya Island, Okinawa, Japan. The structures of these secondary metabolites were elucidated spectroscopically. All compounds were inactive at 30 μg/disc against methicillin-resistant Staphylococcus aureus (MRSA) in combination treatment with a β-lactam drug, meropenem. </p

Aflaquinolones A–G: Secondary Metabolites from Marine and Fungicolous Isolates of <i>Aspergillus</i> spp.

Seven new compounds (aflaquinolones A–G; <b>1</b>–<b>7</b>) containing dihydroquinolin-2-one and terpenoid units have been isolated from two different fungal sources. Two of these metabolites (<b>1</b> and <b>2</b>) were obtained from a Hawaiian fungicolous isolate of <i>Aspergillus</i> sp. (section <i>Flavipedes</i>; MYC-2048 = NRRL 58570), while the others were obtained from a marine <i>Aspergillus</i> isolate (SF-5044) collected in Korea. The structures of these compounds were determined mainly by analysis of NMR and MS data. Relative and absolute configurations were assigned on the basis of NOESY data and ¹H NMR <i>J</i>-values, comparison of calculated and experimental ECD spectra, and analysis of a Mosher’s ester derivative of <b>2</b>. Several known compounds, including alantrypinone, aspochalasins I and J, methyl 3,4,5-trimethoxy-2­((2-((3-pyridinylcarbonyl)­amino)­benzoyl)­amino)­benzoate, and <i>trans</i>-dehydrocurvularin were also encountered in the extract of the Hawaiian isolate

Herquline A, produced by <i>Penicillium herquei</i> FKI-7215, exhibits anti-influenza virus properties

<p>In the course of screening for new anti-influenza virus antibiotics, we isolated herquline A from a culture broth of the fungus, <i>Penicillium herquei</i> FKI-7215. Herquline A inhibited replication of influenza virus A/PR/8/34 strain in a dose-dependent manner without exhibiting cytotoxicity against several human cell lines. It did not inhibit the viral neuraminidase.</p

Total Synthesis of Fusaramin, Enabling Stereochemical Elucidation, Structure–Activity Relationship, and Uncovering the Hidden Antimicrobial Activity against Plant Pathogenic Fungi

Fusaramin (1) was isolated as a mitochondrial inhibitor. However, the fungal producer stops producing 1, which necessitates us to supply 1 by total synthesis. We proposed the complete stereochemical structure based on the biosynthetic pathway of sambutoxin. We have established concise and robust total synthesis of 1, enabling us to determine the complete stereochemical structure and to elucidate the structure–activity relationship, and uncover the hidden antiplant pathogenic fungal activity

Illudins C₂ and C₃ Stimulate Lipolysis in 3T3-L1 Adipocytes and Suppress Adipogenesis in 3T3-L1 Preadipocytes

The secondary metabolites illudins C₂ (<b>1</b>) and C₃ (<b>2</b>), obtained from the culture broth of <i>Coprinus atramentarius</i>, have been shown to possess antimicrobial activity. In the present study, we discovered novel biological activities of <b>1</b> and <b>2</b> in lipolysis of differentiated 3T3-L1 adipocytes and adipogenesis of 3T3-L1 preadipocytes. Compounds <b>1</b> and <b>2</b> exhibit a dose-dependent increase in glycerol release and thereby reduce intracellular lipid accumulation. The stimulatory effects of <b>1</b> and <b>2</b> on lipolysis are prevented by cAMP-dependent protein kinase (PKA) and extracellular signal-regulated kinase (ERK) inhibitors. Compounds <b>1</b> and <b>2</b> down-regulated perilipin and also affected the mRNA and protein levels of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL). However, <b>1</b> and <b>2</b> treatment leads to a significant increase in PKA-mediated phosphorylation of HSL at S563 and S660. In addition, <b>1</b> and <b>2</b> treatment in 3T3-L1 preadipocytes induces down-regulation of the critical transcription factors, CCAAT/enhancer binding protein α and β (C/EBPα and C/EBPβ), and peroxisome proliferator activated receptor γ (PPARγ), which are required for adipogenesis, and accordingly inhibits adipogenesis. These results suggest that <b>1</b> and <b>2</b> might be useful for treating obesity due to their modulatory effects on fat by affecting adipocyte differentiation and fat mobilization

STK295900 inhibits topoisomerases activities.

<p>Supercoiled DNA relaxation assay for (A) topoisomerase 1 (Top 1) and (B) topoisomerase 2 (Top 2). Supercoiled pBR322 plasmid DNA was incubated at 37°C for 30 min with Top 1 enzyme (A) or Top 2α (B) in the presence of various concentrations of indicated compounds. DNA samples were separated by electrophoresis on a 1% agarose gel, stained with ethidium bromide, and visualized by UV light. (−), supercoiled DNA alone; oc, open circular; sc, supercoiled. (C) Antagonistic effect of STK295900 in camptothecin-induced DNA damage. HeLa cells were pretreated with 10 µM of STK295900 for 30 min and then incubated with the indicated concentrations of camptothecin for 1 h. Treated cells were lysed and subjected to immunoblot analyses with antibody against γ-H2A.X. β-actin was used as a loading control. (D) Antagonistic effect of STK295900 on etoposide-induced DNA damage. HeLa cells were pretreated with STK295900 at 10, 20, 30, or 50 µM or ICRF-193 at 10 µM for 30 min. Cells were incubated with 10 µM of etoposide for another 1 h. Treated cells were then lysed and subjected to immunoblot analyses with antibody against γ-H2A.X. β-actin was used as a loading control.</p

Inhibitory effect of STK295900 on proliferation of various cancer cell lines.

<p>Cells were seeded at 1−2×10³ cells in 96 well plates and treated with various concentrations of STK295900. Cell growth was determined by MTT assay for up to 4 days. All experiments were done in triplicates and IC₅₀ was calculated from log-dose-response curves.</p

Comparison of STK295900 with camptothecin, etoposide, and Hoechst 33342 for its effect on the proliferation of various cancer and non-cancer cell lines.

<p>Cells were seeded at 1−2×10³ cells in 96 well plates and treated with various concentrations of STK295900, camptothecin, etoposide, or Hoechst 33342. Cell growth was determined by MTT assay for up to 4 days. All experiments were done at least in triplicates, and IC₅₀ was calculated from dose-response curves.</p

STK295900 does not activate DNA damage checkpoint.

<p>(A) G₂/M transition regulated proteins expression. HeLa cells were treated with STK295900 1 or 5 µM, Camptothecin 10 µM, etoposide 10 µM, or nocodazole 200 ng/ml. After 24 h incubation, cell lysates were prepared for immunoblot analyses with antibodies against phospho-Cdk1 (T161), phospho-Cdk1 (T14), phospho-Cdk1 (Y15), Cdk1, Wee1, and Cdc25C. GAPDH was used as a loading control. (B) DNA damage-checkpoint related proteins. The same lysates used in (A) were subjected to immunoblot analyses with antibodies against phospho-ATM (S1981), ATM, phospho-ATR (S428), ATR, phospho-Chk1 (S345), Chk1, phospho-Chk2 (T68), Chk2, p53, and p21. β-actin was used as a loading control. (C) Immunofluorescence staining for γ-H2A.X. HeLa cells were treated with 1, 5, or 10 µM of STK295900 or 10 µM of ICRF-193, etoposide, and camptothecin for 24 h. Treated cells were then fixed and stained with anti-γ-H2A.X (middle panel). DNA from ICRF-193-, etoposide-, and camptothecin-treated cells was stained with Hoechst 33342 (bottom panel). Images were analyzed on a fluorescence microscope.</p