Epigenetic Manipulation Induced Production of Immunosuppressive Chromones and Cytochalasins from the Mangrove Endophytic Fungus Phomopsis asparagi DHS-48.

A mangrove endophytic fungus Phomopsis asparagi DHS-48 was found to be particularly productive with regard to the accumulation of substantial new compounds in our previous study. In order to explore its potential to produce more unobserved secondary metabolites, epigenetic manipulation was used on this fungus to activate cryptic or silent genes by using the histone deacetylase (HDAC) inhibitor sodium butyrate and the DNA methyltransferase (DNMT) inhibitor 5-azacytidine (5-Aza). Based on colony growth, dry biomass, HPLC, and 1H NMR analyses, the fungal chemical diversity profile was significantly changed compared with the control. Two new compounds, named phaseolorin J (1) and phomoparagin D (5), along with three known chromones (2-4) and six known cytochalasins (6-11), were isolated from the culture treated with sodium butyrate. Their structures, including their absolute configurations, were elucidated using a combination of detailed HRESIMS, NMR, and ECD and 13C NMR calculations. The immunosuppressive and cytotoxic activities of all isolated compounds were evaluated. Compounds 1 and 8 moderately inhibited the proliferation of ConA (concanavalin A)-induced T and LPS (lipopolysaccharide)-induced B murine spleen lymphocytes. Compound 5 exhibited significant in vitro cytotoxicity against the tested human cancer cell lines Hela and HepG2, which was comparative to the positive control adriamycin and fluorouracil. Our finding demonstrated that epigenetic manipulation should be an efficient strategy for the induction of new metabolites from mangrove endophytic fungi.

Immunosuppressive Cytochalasins from the Mangrove Endophytic Fungus Phomopsis asparagi DHS-48.

Three new cytochalasins, phomoparagins A-C (1-3), along with five known analogs (4-8), were isolated from Phomopsis asparagi DHS-48, a mangrove-derived endophytic fungus. Their structures, including their absolute configurations, were elucidated using a combination of detailed HRESIMS, NMR, and ECD techniques. Notably, 1 possessed an unprecedented 5/6/5/8/5-fused pentacyclic skeleton. These compounds were tested for their inhibitory activity against concanavalin A (ConA)/lipopolysaccharide (LPS)-induced spleen lymphocyte proliferation and calcineurin (CN) enzyme. Several metabolites (2 and 4-6) exhibited fascinating inhibitory activities with a relatively low toxicity. Furthermore, 2 was demonstrated to inhibit ConA-stimulated activation of NFAT1 dephosphorylation and block NFAT1 translocation in vitro, subsequently inhibiting the transcription of interleukin-2 (IL-2). Our results provide evidence that 2 may, at least partially, suppress the activation of spleen lymphocytes via the CN/NFAT signaling pathway, highlighting that it could serve as an effective immunosuppressant that is noncytotoxic and natural.

A new cytotoxic 19-nor-cardenolide from the latex of Antiaris toxicaria.

A new nor-cardenolide, named toxicarioside H (1), was isolated from the latex of Antiaris toxicaria (Pers.) Lesch (Moraceae). Its structure was elucidated on the basis of HRFAB-MS and spectroscopic techniques (IR, UV, 1D and 2D NMR). Compound 1 showed significant cytotoxicity against K562, SGC-7901, SMMC-7721, and HeLa cell lines in vitro by MTT method.

Two new cytotoxic cardenolides from the latex of Antiaris toxicaria.

Two new cardenolides, toxicarioside F (1) and toxicarioside G (2), were isolated from the latex of Antiaris toxicaria (Pers.) Lesch (Moraceae). Their structures were elucidated on the basis of spectral data and chemical evidence. Compounds 1 and 2 showed significant cytotoxicity against K562, SGC-7901, SMMC-7721, and HeLa cell lines in vitro by the MTT method.

Oxidative cyclization of N-acylhydrazones. Development of highly selective turn-on fluorescent chemodosimeters for Cu2+.

A series of N-acylhydrazones were synthesised and found to be "turn-on" fluorescent chemodosimeters for Cu(2+). Among the tested transition metal ions such as Cu(2+), Pb(2+), Zn(2+), Cd(2+), Hg(2+), and Ni(2+), a prominent fluorescence enhancement of up to 1000-fold was only observed for Cu(2+) in acetonitrile (CH(3)CN). This was indicated by an onset of unprecedented structured emission. Detailed experiments established that the highly Cu(2+) selective fluorescence enhancement resulted from an oxidative cyclization by Cu(2+)of the originally nonfluorescent N-acylhydrazones into highly fluorescent rigid 1,3,4-oxadiazoles, n-dope type blocks in optoelectronic materials. The chemodosimeters can be applied to sense Cu(2+) at nM levels in CH(3)CN and sub-microM levels in neutral aqueous environments, despite a slower response in the latter case. It is expected that these redox-based chemodosimeters might be of general applicability.

Influence of N-substituent and solvent on internal conversion in 1-aminonaphthalenes.

N-Methyl-N-methoxycarbonylmethyl-1-aminonaphthalene (MMAN) and N,N-dimethoxycarbonylmethyl-1-aminonaphthalene (DCAN) were synthesized and their fluorescence and absorption spectra in solvents of varied polarity were investigated and compared to those of 1-dimethylaminonaphthylene (DMAN). The data were discussed in terms of the N-substitution effects on the internal conversion (IC). Results showed that the IC was enhanced when the N-methyl group in DMAN was replaced by N-CH2CO2CH3.

A highly selective charge transfer fluoroionophore for Cu2+.

A dual fluorescent charge transfer fluoroionophore (1) with its ionophore incorporated in the electron acceptor was developed and was found to show a highly selective fluorescent response to Cu2+ with a dramatic enhancement in its CT emission.

A novel thiourea-based dual fluorescent anion receptor with a rigid hydrazine spacer.

[structure: see text] A neutral receptor with a rigid hydrazine spacer, N-p-(dimethylamino)benzamido-N'-phenylthiourea, was prepared, and its dual fluorescence in acetonitrile was found to show response toward the presence of anions such as AcO(-), H(2)PO(4)(-), HSO(4)(-), Br(-), Cl(-), F(-), and ClO(4)(-) with high sensitivity and selectivity toward AcO(-).