Bing-Nan Han

Hippolachnin A, a New Antifungal Polyketide from the South China Sea Sponge Hippospongia lachne

Hippolachnin A (1), a polyketide possessing an unprecedented carbon skeleton with a four-membered ring, was isolated from the South China Sea sponge Hippospongia lachne. The structure was elucidated using MS and NMR spectroscopic analyses, and the absolute configuration was determined using a calculated ECD method. Hippolachnin A demonstrated potent antifungal activity against three pathogenic fungi, Cryptococcus neoformans, Trichophyton rubrum, and Microsporum gypseum, with a MIC value of 0.41 μM for each fungus.

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.

New Hippolide Derivatives with Protein Tyrosine Phosphatase 1B Inhibitory Activity from the Marine Sponge Hippospongia lachne

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.

Relative and absolute stereochemistry of diacarperoxides: antimalarial norditerpene endoperoxides from marine sponge Diacarnus megaspinorhabdosa.

Five new norditerpene endoperoxides, named diacarperoxides H–L (1–5), and a new norditerpene diol, called diacardiol B (6), were isolated from the South China Sea sponge, Diacarnus megaspinorhabdosa. Their structures, including conformations and absolute configurations, were determined by using spectroscopic analyses, computational approaches and chemical degradation. Diacarperoxides H–J (1–3) showed some interesting stereochemical issues, as well as antimalarial activity.

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.

Dysidinoid A, an Unusual Meroterpenoid with Anti-MRSA Activity from the South China Sea Sponge Dysidea sp.

An unusual meroterpenoid, dysidinoid A (1), was isolated from the South China Sea sponge Dysidea sp. Its structure was elucidated by extensive spectroscopic methods including HRESIMS and 2D NMR, and its absolute configuration was determined by single-crystal X-ray diffraction analysis. Dysidinoid A (1) is the first meroterpenoid from Nature bearing a 9,4-friedodrime skeleton and a 2,5-dionepyrrole unit. Dysidinoid A (1) showed potent antibacterial activity against two strains of pathogenic bacteria methicillin-resistant Staphylococcus aureus (MRSA) with MIC90 values of 8.0 μg/mL against both.

Hypocrol A, a new tyrosol derivative from a sponge-derived strain of the fungus Hypocrea koningii

Abstract In continuation of our search for new antibacterial and antioxidant metabolites from sponge-derived fungi, one new tyrosol derivative, hypocrol A (1), together with four known congeners, trichodenol B (2), 4-hydroxyphenethyl acetate (3), 4-hydroxyphenethyl tetradecanoate (4) and 1-oleyltyrosol (5), was isolated from the strain Hypocrea koningii PF04. Their planar structures were unequivocally elucidated by spectroscopic methods and comparison with the literature data. All the compounds displayed weak antibacterial activities against Staphylococcus aureus, methicillin-resistant S. aureus and Escherichia coli, whereas compounds 1 and 2 exhibited a moderate antioxidant efficacy in the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay with IC50 values of 48.5 and 97.4 μg/mL, respectively. Graphical abstract

N-terminal α-amino group modification of antibodies using a site-selective click chemistry method

ABSTRACT Site-specific conjugation of small molecules to antibody molecules is a promising strategy for generation of antibody-drug conjugates. In this report, we describe the successful synthesis of a novel bifunctional molecule, 6-(azidomethyl)-2-pyridinecarboxyaldehyde (6-AM-2-PCA), which was used for conjugation of small molecules to peptides and antibodies. We demonstrated that 6-AM-2-PCA selectively reacted with N-terminal amino groups of peptides and antibodies. In addition, the azide group of 6-AM-2-PCA enabled copper-free click chemistry coupling with dibenzocyclooctyne-containing reagents. Bifunctional 6-AM-2-PCA mediated site-specific conjugation without requiring genetic engineering of peptides or antibodies. A key advantage of 6-AM-2-PCA as a conjugation reagent is its ability to modify proteins in a single step under physiological conditions that are sufficiently moderate to retain protein function. Therefore, this new click chemistry-based method could be a useful complement to other conjugation methods.

Two Marine Cyanobacterial Aplysiatoxin Polyketides, Neo-debromoaplysiatoxin A and B, with K+ Channel Inhibition Activity

The isolation and structure elucidation of two cyanobacterial debromoaplysiatoxin (DAT) analogues, neo-debromoaplysiatoxin A (1) and neo-debromoaplysiatoxin B (2), were reported and found to possess 6/10/6 and 6/6/6 fused-ring systems, respectively, which are rarely seen among aplysiatoxins. Both compounds exhibited potent blocking activity against Kv1.5 with IC50 values of 6.94 ± 0.26 and 0.30 ± 0.05 μM, respectively. These findings suggest the potential of aplysiatoxin analogues in modulating ionic channels and also provide links between the DAT target, protein kinase C, and cell regulation.