Polyketides from the Cultured Lichen Mycobiont of a Vietnamese <i>Pyrenula</i> sp.

A spore-derived mycobiont of a crustose <i>Pyrenula</i> sp. lichen collected in Vietnam was cultivated on a malt-yeast extract medium supplemented with 10% sucrose. Chemical investigation of the cultivated colonies led to the isolation of eight new alkylated decalin-type polyketides (<b>1</b>–<b>8</b>) along with three known compounds. The structures of these compounds were elucidated by spectroscopic and chemical means. This is the first instance of this type of polyketide being isolated from a cultured lichen mycobiont. The isolated polyketides <b>1</b> and <b>7</b> exhibited inhibitory activities against mammalian DNA polymerases α and β with IC₅₀ values ranging from 8.1 to 19.5 μM. Compound <b>1</b> showed cytotoxic effects against the HCT116 human colon carcinoma cultured cell line with an IC₅₀ value of 6.4 ± 0.7 μM

Bioactive Dihydronaphthoquinone Derivatives from <i>Fusarium solani</i>

New dihydronaphthoquinone derivatives, karuquinone A (<b>1</b>), karuquinone B (<b>2</b>), and karuquinone C (<b>3</b>), were isolated from a fungal culture broth of <i>Fusarium solani</i>. The structures were determined by interpretation of spectroscopic data (1D/2D NMR, MS, and IR). Three known compounds, javanicin (<b>4</b>), 2,3-dihydro-5-hydroxy-8-methoxy-2,4-dimethylnaphtho­[1,2-<i>b</i>]­furan-6,9-dione (<b>5</b>), and 5-hydroxydihydrofusarubin C (<b>6</b>), were also isolated. The six isolated compounds were tested for cytotoxicity against three human cancer cell lines and a human umbilical vein endothelial cell (HUVEC) line. Of these, karuquinone A exhibited the strongest cytotoxic activity. Karuquinone B did not affect the proliferation of the cancer cell lines but did inhibit the proliferation of HUVEC. Additionally, we demonstrated that karuquinone A induces apoptosis in cancer cells through the generation of reactive oxygen species (ROS)

Structure of plumbagin (1), 5-<i>O</i>-acyl plumbagins (2), vitamin K₃ (3), juglone (4), and 5-<i>O</i>-acyl juglones (5).

<p>“R” represents a saturated or unsaturated alkyl group in 5-<i>O</i>-acyl plumbagins (<b>2</b>) and 5-<i>O</i>-acyl juglones (<b>5</b>).</p

Stability of C18:1-acyl plumbagin (2f) and C18:1-acyl juglone (5f) under basic conditions.

<p>C18:1-acyl plumbagin (<b>2f</b>) (A) and C18:1-acyl juglone (<b>5f</b>) (B) were treated with 1 equivalent of Triton B in 1,4-dioxane and MeOH. The mixtures were monitored by UV-vis spectroscopy over time. Conditions: 1.1×10⁻³ M, 25°C, light path length = 1 mm.</p

Synthesis, Photochemical Properties, and Cytotoxicities of 2<i>H</i>‑Naphtho[1,2‑<i>b</i>]pyran and Its Photodimers

A 2<i>H</i>-naphtho­[1,2-<i>b</i>]­pyran, prepared by dimerization of 2-bromo-3-methyl-1,4-naphthoquinone and <i>O</i>-methylation, readily undergoes solid-state [2 + 2] photodimerization to give a photodimer in excellent yield and with excellent selectivity. Retro [2 + 2] cycloaddition can be achieved by irradiation of a solution of the photodimer in chloroform. Interestingly, the 2<i>H</i>-naphtho­[1,2-<i>b</i>]­pyran dimerizes with a skeletal rearrangement to afford 2,5-dihydro-1-benzoxepin dimers upon irradiation in methanol or via irradiation with hexamethylditin. Furthermore, treatment of the resulting dimers with triethylamine regenerates the 2<i>H</i>-naphtho­[1,2-<i>b</i>]­pyran monomer. Significant differences in the color, fluorescence, and cytotoxic properties of the monomer and dimers were observed

Relationship between mammalian pol inhibitory activities versus human cancer cell proliferation inhibition by plumbagin (1) and 5-<i>O</i>-acyl plumbagins (2a–j).

<p>X-axis indicates mammalian pol relative activity at 10 µM compound. (A) Calf pol α, (B) human pol γ, (C) human pol κ, and (D) human pol λ. Y-axis indicates rate of HCT116 human colon carcinoma cell proliferation at 100 µM compound. These data are based on <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088736#pone-0088736-g004" target="_blank">Figs. 4</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088736#pone-0088736-g005" target="_blank">5</a>; correlation coefficient values are shown in each panel.</p

LD₅₀ values of C18:1-acyl plumbagin (<b>2f</b>) on the proliferation of human cancer cells.

<p>The nine human cancer cell lines were incubated with C18:1-acyl plumbagin (<b>2f</b>) for 48 h. Cell viability was determined by MTT assay, and this viability in the absence of an inhibitor (control) was taken as 100%; data, mean ± SD (n = 5).</p>**<p><i>P</i><0.01 vs. controls.</p

Inhibitory effects of plumbagin (1) and 5-<i>O</i>-acyl plumbagins (2a–j) on the activity of mammalian pols.

<p>Each compound (10 µM) was incubated with calf pol α (B-family pol), human pol γ (A-family pol), human pol κ (Y-family pol), and human pol λ (X-family pol) (0.05 units each). Pol activity in the absence of the compound (control) was taken as 100%, and the relative activity is shown. Data are shown as the mean ± SD (n = 3). ** <i>P</i><0.01 and * <i>P</i><0.05 vs. controls.</p