Bin-Bin Gu

(±)-Quassidines I and J, Two Pairs of Cytotoxic Bis-β-carboline Alkaloid Enantiomers from Picrasma quassioides

(±)-Quassidines I (1) and J (2), two pairs of new bis-β-carboline alkaloid enantiomers, were isolated from the stems of Picrasma quassioides. Their structures were determined by the analysis of spectroscopic data, including HRESIMS and 2D NMR, and confirmed by single-crystal X-ray diffraction analysis. The racemic mixtures of 1 and 2 were resolved into two pairs of enantiomers, (+)-S-1a and (-)-R-1b and (+)-S-2a and (-)-R-2b, by HPLC using a chiral Daicel IB-3 column, respectively, which represents the first successful example to resolve bis-β-carboline racemic mixtures. The absolute configurations of the two pairs of enantiomers were determined by comparison between the calculated and experimental ECD spectra. The cytotoxicity evaluation revealed that (+)-S-1a and (+)-S-2a showed more potent cytotoxicity against human cervical HeLa and gastric MKN-28 cancer cell lines with IC50 values of 4.03-6.30 μM than their enantiomers with IC50 values of 9.64-12.3 μM; however, the two (+)-S-quassidines showed similar activities to their enantiomers against the mouse melanoma B-16 cancer cell line.

Dysiherbols A-C and Dysideanone E, Cytotoxic and NF-κB Inhibitory Tetracyclic Meroterpenes from a Dysidea sp. Marine Sponge.

Four new tetracyclic meroterpnes, dysiherbols A-C (1-3) and dysideanone E (4), were isolated from a Dysidea sp. marine sponge collected from the South China Sea. Their complete structures and absolute configurations were unambiguously determined by a combination of NMR spectroscopic data, ECD calculations, and single-crystal X-ray diffraction analysis. Within the sesquiterpene quinol structures, dysiherbols A-C possess an intriguing 6/6/5/6-fused tetracyclic carbon skeleton. The NF-κB inhibitory and cytotoxic activity evaluation disclosed that dysiherbol A (1) showed potent activity with respective IC50 values of 0.49 and 0.58 μM, which were about 10-fold and 20-fold more potent than those of dysiherbols B (2) and C (3), which feature hydroxy and ketone carbonyl groups at the C-3 position.

Sesquiterpene Quinones/Hydroquinones from the Marine Sponge Spongia pertusa Esper

Nine new sesquiterpene quinones/hydroquinones (1-7, 10, and 12), three solvent-generated artifacts (8, 9, and 11), and three known compounds, 5-epi-smenospongine (13), smenospongine (14), and smenospongiadine (15), were isolated from the marine sponge Spongia pertusa Esper. The planar structures of the new compounds were elucidated on the basis of spectroscopic analyses. Their absolute configurations were determined by comparison between the calculated and experimental ECD spectra. In the cytotoxicity bioassay, compounds 13-15 exhibited activities against the human cancer cell lines U937, HeLa, and HepG2, with most potent cytotoxicities to U937 cells with IC50 values of 2.8, 1.5, and 0.6 μM, respectively. In addition, compound 6 displayed CDK-2 affinity with a Kd value of 4.8 μM in a surface plasmon resonance assay.

Bioactive sesquiterpene quinols and quinones from the marine sponge Dysidea avara

Four new sesquiterpene quinols, dysiquinols A–D (1–4), and four new sesquiterpene quinones, (5S,8S,9R,10S)-18-ethoxyneoavarone (5), (5S,8S,9R,10S)-19-ethoxyneoavarone (6), (5R,8R,9S,10R)-18-ethoxyavarone (7), and (5R,8R,9S,10R)-19-ethoxyavarone (8), together with a known compound, avarol (9), were isolated from the South China Sea marine sponge Dysidea avara. The planar structures of new compounds were elucidated by interpretation of HRESIMS and 2D NMR spectroscopic data, and their absolute configurations were determined by comparison between the calculated and experimental ECD spectra. The cytotoxicity of 1–9 against human myeloma cancer cell line NCI-H929 and their NF-κB inhibitory activity were evaluated. Among these metabolites, dysiquinol D (4) showed the most potent cytotoxic and NF-κB inhibitory activities with IC50 values of 2.8 and 0.81 μM, respectively.

Unusual Anti-allergic Diterpenoids from the Marine Sponge Hippospongia lachne

Hipposponlachnins A (1) and B (2), possessing an unprecedented tetracyclo [9.3.0.02,8.03,7] tetradecane ring system, and the probable biogenetic precursor [3, (1R*,2E,4R*,7E,10S*,11S*,12R*)-10, 18-diacetoxydolabella-2,7-dien-6-one] of 1‒2 were isolated from the South China Sea marine sponge Hippospongia lachne. The structures of the novel compounds were determined using integrated spectroscopic methods in combination with single-crystal X-ray diffraction analysis. Compounds 1‒2 showed potent inhibitory activity on the release of β-hexosaminidase, a biomarker for degranulation, as well as the production of pro-inflammatory cytokine IL-4 and lipid mediator LTB4 in DNP-IgE-stimulated RBL-2H3 cells.

New Metabolites from the South China Sea Sponge Diacarnus megaspinorhabdosa

Chemical investigation on CH2Cl2 extract of the marine sponge Diacarnus megaspinorhabdosa resulted in the isolation of two new farnesylacetone derivatives 1-2, a new γ-lactone 3, a known dinorditerpenone 4 and four known norsesterterpene peroxides 5-8. Their structures were elucidated by using one and two dimensional (1D and 2D)-NMR, high resolution-electrospray ionization (HR-ESI)-MS, and comparison with the literature. Compounds 1 and 2 were cis/trans-olefinic isomers and determined through nuclear Overhauser effect spectroscopy (NOESY) experiment. The absolute configuration of 3 was established by comparison of circular dichroism (CD) data with known lactones. The cytotoxic activities of the compounds were evaluated against five cancer cell lines, and compound 3 showed moderate cytotoxicity activities against cancer cell lines HeLa, H446, NCI-H460, SGC-7901 and MCF-7, with IC50 values in the range of 18.5 to 47.1 µM.

Dysivillosins A–D, Unusual Anti-allergic Meroterpenoids from the Marine Sponge Dysidea villosa

Four unusual meroterpenoids, dysivillosins A–D (1–4), were isolated from an organic extract of the marine sponge Dysidea villosa collected from the South China Sea. Their planar structures were determined by 1D and 2D NMR and HRESIMS techniques, while the relative and absolute configurations were elucidated by NOESY experiments and comparison between the calculated and experimental ECD spectra. To the best of our knowledge, dysivillosins A–D are the first examples of terpene-polyketide-pyridine hybrid metabolites from the nature. Anti-allergic activity evaluation showed that compounds 1–4 potently inhibited the release of β-hexosaminidase, a marker of degranulation, in a dose-dependent manner with IC50 values of 8.2–19.9 μM. Additionally, the four meroterpenoids could downregulate the production of lipid mediator leukotrienes B4 (LTB4) and pro-inflammatory cytokine interleukin-4 (IL-4) in the antigen-stimulated RBL-2H3 mast cells. Further biological investigations revealed that dysivillosin A (1) could suppress the phosphorylation of Syk and PLCγ1 in IgE/FcɛRI/Syk signaling pathway, which resulted in the inhibition of degranulation and the downregulation of LTB4 and IL-4 production in mast cells.

Structure, absolute configuration, and variable-temperature 1H-NMR study of (±)-versiorcinols A–C, three racemates of diorcinol monoethers from the sponge-associated fungus Aspergillus versicolor 16F-11

Three racemates of diorcinol monoethers, (±)-versiorcinols A–C (1–3), were initially isolated from the fungus Aspergillus versicolor 16F-11. The structures of versiorcinols B and C were elucidated by comprehensive spectroscopic analysis, while the structure of versiorcinol A was elucidated on the basis of quantum-chemical NMR chemical shifts, supported by DP4 probability analysis, and DU8 proton–proton spin–spin coupling constants (SSCCs) calculations in consortium with extensive experimental NMR analysis. The absolute configurations of the enantiomers (+)-1 and (−)-1, (+)-2 and (−)-2, and (+)-3 and (−)-3 were assigned from ECD calculations. At very low temperatures, the 1H-NMR spectra of 1–3 revealed doubling of signals, which suggested the presence of two conformers in solution. Variable-temperature (VT) 1H-NMR studies supported this hypothesis.

A new asymmetric diketopiperazine dimer from the sponge-associated fungus Aspergillus versicolor 16F-11

A new asymmetric diketopiperazine dimer, Asperflocin (1), has been isolated from the fungus Aspergillus versicolor 16F-11. Its structure was determined by virtue of detailed spectroscopic analysis, Marfeys method, and 13 C NMR chemical shifts, [α]25D , and TDDFT/ECD calculations. Cytotoxic activity test showed that 1 has moderate cytotoxic activity against A375 cell line with IC50 value of 10.29 ± 2.37 μM.

Preussins with Inhibition of IL-6 Expression from Aspergillus flocculosus 16D-1, a Fungus Isolated from the Marine Sponge Phakellia fusca

New pyrrolidine alkaloids, preussins C-I (1-7) and (11 R)/(11 S)-preussins J and K (8 and 9), were isolated from the sponge-derived fungus Aspergillus flocculosus 16D-1. The structures and configurations of these preussins were elucidated by detailed spectroscopic analysis, modified Moshers method, and comparisons with literature data. These compounds showed strong to moderate inhibitory activity toward IL-6 production in lipopolysaccharide-induced THP-1 cells with IC50 values ranging from 0.11 to 22 μM, but were inactive against normal tumor cell lines and fungi.