Yang-Hua Yi

Estrogen‐dependent cancers (breast, endometrial, and ovarian) are among the leading causes of morbidity and mortality in women worldwide. Aromatase is the main enzyme that catalyzes the biosynthesis of estrogen, which drives proliferation, and antiestrogens can inhibit the growth of these estrogen‐dependent cancers. Hu‐17, an aromatase inhibitor, is a novel small‐molecule compound that suppresses viability of and promotes apoptosis in ovarian cancer cells. Therefore, this study aimed to predict targets of Hu‐17 and assess its intracellular signaling in ovarian cancer cells. Using the Similarity Ensemble Approach software to predict the potential mechanism of Hu‐17 and combining phospho‐proteome arrays with western blot analysis, we observed that Hu‐17 could inhibit the ERK pathway, resulting in reduced estrogen synthesis in KGN cells, a cell line derived from a patient with invasive ovarian granulosa cell carcinoma. Hu‐17 reduced the expression of CYP19A1 mRNA, responsible for producing aromatase, by suppressing the phosphorylation of cAMP response element binding‐1. Hu‐17 also accelerated aromatase protein degradation but had no effect on aromatase activity. Therefore, Hu‐17 could serve as a potential treatment for estrogen‐dependent cancers albeit further investigation is warranted.

Seven new briarane diterpenoids, gemmacolides AZ–BF (1–7), were isolated together with eight known analogues (8–15) from the South China gorgonian Dichotella gemmacea. Their structures were elucidated based on detailed spectroscopic analysis and a comparison with reported data. In an in vitro bioassay, these compounds exhibited different levels of growth inhibition activity against A549 and MG63 cells, giving continuous evidences about the biological contribution of functional groups at C-2, C-12, C-13, and C-16. These compounds were also evaluated for their antibacterial and antifungal activities. Compound 8 exhibited a potential antibacterial activity against both Gram-positive bacterium Bacillus megaterium and Gram-negative bacterium Escherichia coli.

Five new sesterterpenoids, compounds 1–5, have been isolated from the sponge Hippospongia lachne off Yongxing Island in the South China Sea. The structures of compounds 1–5 were elucidated through extensive spectroscopic analysis, including HRMS, 1D, and 2D NMR experiments. The stereochemistry, including absolute configurations of these compounds, was determined by spectroscopic, chemical, and computational methods. Compounds 1 and 5 showed moderate protein tyrosine phosphatase 1B (PTP1B) inhibitory activities with IC₅₀ values of 5.2 μM and 8.7 μM, respectively, more potent than previously reported hippolides.

Eighteen new 11,20-epoxy-3Z,5E-dien briaranes, gemmacolides AA–AR (1–1 8), were isolated together with three known analogs, dichotellides F (19) and I (2 0), and juncenolide C (2 1), from the South China Sea gorgonian Dichotella gemmacea. The structures of the compounds were elucidated by detailed spectroscopic analysis and comparison with reported data. The absolute configuration was determined based on the ECD experiment. In the in vitro bioassay, compounds 1–3, 5, 6, 8–12, and 14–19 exhibited different levels of growth inhibition activity against A549 and MG63 cell lines. Preliminary structure-activity analysis suggests that 12-O-isovalerate may increase the activity whereas 13- or 14-O-isovalerate may decrease the activity. Contribution of substitutions at C-2 and C-16 remains uncertain.

Seven new polyoxygenated steroids (1–7) were isolated together with seven known analogues (8–1 4) from the South China Sea soft coral, Sarcophyton sp. The structures of the new compounds were identified on the basis of extensive spectroscopic analysis and comparison with reported data. All the steroids are characterized with 3β,5α,6β-hydroxy moiety, displaying carbon skeletons of cholestane, ergostane, gorgostane and 23,24-dimethyl cholestane. In the in vitro bioassay, metabolites exhibited different levels of antimicrobial activity against bacterial species Escherichia coli and Bacillus megaterium, and fungal species Microbotryum violaceum and Septoria tritici. No inhibition was detected towards microalga Chlorella fusca. Preliminary structure-activity analysis suggests that the 11α-acetoxy group may increase both antibacterial and antifungal activities. The terminal-double bond and the cyclopropane moiety at the side chain may also contribute to the bioactivity.

Four known hydroxyanthraquinones (1–4) together with four new derivatives having a tetralone moiety, namely coniothyrinones A–D (5–8), were isolated from the culture of Coniothyrium sp., an endophytic fungus isolated from Salsola oppostifolia from Gomera in the Canary Islands. The structures of the new compounds were elucidated by detailed spectroscopic analysis and comparison with reported data. The absolute configurations of coniothyrinones A (5), B (6), and D (8) were determined by TDDFT calculations of CD spectra, allowing the determination of the absolute configuration of coniothyrinone C (7) as well. Coniothyrinones A (5), B (6), and D (8) could be used as ECD reference compounds in the determination of absolute configuration for related tetralone derivatives. This is the first report of anthraquinones and derivatives from an isolate of the genus Coniothyrium sp. These compounds showed inhibitory effects against the fungus Microbotryum violaceum, the alga Chlorella fusca, and the bacteria Escherichia coli and Bacillus megaterium. Chirality 25:141–148, 2013.

Two new alkene sulfates, (5Z)‐dec‐5‐en‐1‐yl sulfate (4) and (3E)‐dec‐3‐en‐1‐yl sulfate (5), together with three known sulfated alkanes, 2,6‐dimethylheptyl sulfate (1), octyl sulfate (2), and decyl sulfate (3), were isolated from the sea cucumber Apostichopus japonicus. The structures of the new compounds 4 and 5 were elucidated by spectroscopic analysis, including ¹H‐, ¹³C‐, and 2D‐NMR, ESI‐MS, and HR‐ESI‐MS. Compounds 2 and 3 were isolated from natural sources for the first time. In preliminary bioassays in vitro, compounds 4 and 5 showed antibacterial, antifungal, and cytotoxic activities.

To study the new antifungal active triterpene glycosides of sea cucumber Holothuria scabra. Triterpene glycosides from Holothuria scabra were separated and purified by silica gel chromatography, reversed-phase silica gel chromatography and RP-HPLC. Their structures were elucidated on the basis of spectral data and chemical evidence. Three triterpene glycosides were identified as scabraside A (1), echinoidea A (2) and holothurin A1 (3). Scabraside A (1) is a new triterpene glycoside, and compounds 2 and 3 were isolated from Holothuria scabra for the first time. They showed antifungal activities (1 < or = MIC80 < or = 16 microg mL(-1)).