Hao-Bing Yu

Dysideanones A-C, unusual sesquiterpene quinones from the South China Sea sponge Dysidea avara.

Dysideanones A-C (1-3), three unusual sesquiterpene quinones with unprecedented carbon skeletons, were isolated from the South China Sea sponge Dysidea avara. Their structures including absolute configurations were determined by a combination of spectroscopic analyses and calculated ECD spectra. Within the sesquiterpene quinone structures, dysideanones A (1) and B (2) share an unprecedented 6/6/6/6-fused tetracyclic carbon skeleton, while dysideanone C (3) possesses an unusual 6/6/5/6-fused tetracyclic core. Dysideanone B (2) showed cytotoxicity against two human cancer cell lines, HeLa and HepG2, with IC50 values of 7.1 and 9.4 μM, respectively.

Simplextones A and B, Unusual Polyketides from the Marine Sponge Plakortis simplex

Two novel polyketides, simplextones A (1) and B (2), were isolated from the sponge Plakortis simplex. Their structures were established by spectroscopic methods. The absolute configurations were assigned by modified Moshers method, X-ray crystallographic analysis, and quantum mechanical calculation of the electronic circular dichroism (ECD) spectrum. Compounds 1 and 2 featured an unprecedented polyketide skeleton via the connection of a single carbon-carbon bond to form a cyclopentane. These compounds also exhibited moderate cytotoxicity.

(±)-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.

Cytotoxic aaptamine derivatives from the South China Sea sponge Aaptos aaptos.

Nine new aaptamine derivatives (1-9), together with three known related compounds (10-12), have been isolated from the South China Sea sponge Aaptos aaptos. The structures of all compounds were unambiguously elucidated on the basis of spectroscopic analyses. Structurally, compound 1 possesses a piperidinyl group fused to a demethyl(oxy)aaptamine moiety, whereas compounds 3-6 share an imidazole-fused 1H-benzo[de][1,6]naphthyridin-2(4H)-one skeleton. The cytotoxic activities of the compounds were evaluated against various human cancer cell lines, and compounds 2, 8, 11, and 12 showed potent cytotoxicities against HL60, K562, MCF-7, KB, HepG2, and HT-29 cells, with IC50 values in the range of 0.03 to 8.5 μM.

Cytotoxic Bryostatin Derivatives from the South China Sea Bryozoan Bugula neritina.

Four new macrocyclic lactones, bryostatin 21 (1) and 9-O-methylbryostatins 4, 16, and 17 (2-4), together with three known related compounds, bryostatins 4, 16, and 17 (5-7), have been isolated from an extract of the South China Sea bryozoan Bugula neritina. The structures of all compounds were unambiguously elucidated using detailed spectroscopic analysis. Structurally, the presence of a single methyl group at C-18 in compound 1 has not been observed before for known bryostatins. The isolated macrolides exhibited inhibitory effects against a small panel of human cancer cell lines.

Woodylides A–C, New Cytotoxic Linear Polyketides from the South China Sea Sponge Plakortis simplex

Three new polyketides, woodylides A–C (1–3), were isolated from the ethanol extract of the South China Sea sponge Plakortis simplex. The structures were elucidated by spectroscopic data (IR, 1D and 2D NMR, and HRESIMS). The absolute configurations at C-3 of 1 and 3 were determined by the modified Mosher’s method. Antifungal, cytotoxic, and PTP1B inhibitory activities of these polyketides were evaluated. Compounds 1 and 3 showed antifungal activity against fungi Cryptococcus neoformans with IC50 values of 3.67 and 10.85 µg/mL, respectively. In the cytotoxicity test, compound 1 exhibited a moderate effect against the HeLa cell line with an IC50 value of 11.2 µg/mL, and compound 3 showed cytotoxic activity against the HCT-116 human colon tumor cell line and PTP1B inhibitory activity with IC50 values of 9.4 and 4.7 µg/mL, respectively.

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.

New Furan and Cyclopentenone Derivatives from the Sponge-Associated Fungus Hypocrea Koningii PF04

Two new furan derivatives, hypofurans A and B (1 and 2), and three new cyclopentenone derivatives, hypocrenones A–C (3–5), along with seven known compounds (6–12), were isolated from a marine fungus Hypocrea koningii PF04 associated with the sponge Phakellia fusca. Among them, compounds 10 and 11 were obtained for the first time as natural products. The planar structures of compounds 1–5 were elucidated by analysis of their spectroscopic data. Meanwhile, the absolute configuration of 1 was determined as 2R,3R by the comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. All the isolates were evaluated for their antibacterial and antioxidant activity. Compounds 1, 10, and 12 all showed modest antibacterial activity against Staphylococcus aureus ATCC25923 (MIC, 32 μg/mL). In addition, compounds 1, 10 and 11 exhibited moderate DPPH radical scavenging capacity with IC50 values of 27.4, 16.8, and 61.7 µg/mL, respectively.

Dysidaminones A–M, cytotoxic and NF-κB inhibitory sesquiterpene aminoquinones from the South China Sea sponge Dysidea fragilis

Dysidaminones A–M (1–13), thirteen new sesquiterpene aminoquinones, along with six known ones (14–19), were isolated from the South China Sea sponge Dysidea fragilis. The new structures were determined by extensive spectroscopic analyses, the absolute configurations of 1 and 2 were determined by single-crystal X-ray diffraction analysis, and the absolute configurations of 3–13 were assigned by comparing their CD spectra with those of 1 and 2. Dysidaminones C (3), E (5), H (8), and J (10), 18-methylaminoavarone (14), and 18-aminoavarone (16) showed cytotoxicity against mouse B16F10 melanoma and human NCI-H929 myeloma, HepG2 hepatoma, and SK-OV-3 ovarian cancer cell lines. In addition, these six cytotoxic compounds also exhibited NF-κB inhibitory activity with IC50 values of 0.05–0.27 μM. Preliminary structure–activity relationship analysis indicated that 18-aminosubstituted sesquiterpene quinones with exocyclic double bond (Δ4,11) are cytotoxic agents and NF-κB inhibitors.

PPAR Modulating Polyketides from a Chinese Plakortis simplex and Clues on the Origin of Their Chemodiversity.

Fifteen polyketides, including the first hydroxylated plakortone (12) and plakdiepoxide (15), the first polyketide to embed a vicinal diepoxide, have been isolated from the Chinese sponge Plakortis simplex. The structures of the new metabolites were elucidated by analysis of spectroscopic data, Moshers derivatization, and DFT computational calculations. The reactivity of the major endoperoxide of this sponge was investigated, suggesting that furan, furanylidene, and plakilactone derivatives, well-known classes of natural products, could actually be chemical degradation products. Plakdiepoxide is a potent and selective modulator of peroxisome proliferator-activated receptor (PPAR)-γ, while the diunsaturated C12 fatty acid monotriajaponide (13) activates both PPAR-α and PPAR-γ, a dual activity of potential great importance for the treatment of metabolic disorders.