Huayue Li

Bioactive metabolites from the sponge-derived fungus Aspergillus versicolor

As part of an ongoing search for bioactive metabolites from the fungus Aspergillus versicolor derived from a marine sponge Petrosia sp., an aromatic polyketide derivative (1), two xanthones (2 and 3), and five anthraquinones (4–8) were isolated by bioactivity-guided fractionation. The gross structures were determined based on the NMR and MS spectroscopic data, and the absolute configurations were defined by comparison of optical rotation data with those of reported. Compounds 2, 4, 5, and 7 exhibited significant cytotoxicity against five human solid tumor cell lines (A-549, SK-OV-3, SK-MEL-2, XF-498, and HCT-15) with IC50 values in the range of 0.41–4.61 μg/mL. Compounds 4 and 7 exhibited antibacterial activity against several clinically isolated Gram-positive strains with MIC values of 0.78–6.25 μg/mL.

Marine-derived Aspergillus species as a source of bioactive secondary metabolites.

This report reviews biologically active secondary metabolites from marine-derived members of the fungal genus Aspergillus. Pharmacological activities and biological roles of the secondary metabolites from marine-derived Aspergillus spp. were addressed in respect of pharmaceutical potential.

Anti-inflammatory amino acid derivatives from the ascidian Herdmania momus.

Four new amino acid derivatives, herdmanines A-D (1-4), were isolated from the marine ascidian Herdmania momus. Herdmanines A-C contain the unusual D-form of arginine. Compounds 3 and 4 had a moderate suppressive effect on the production of NO, with IC₅₀ values of 96 and 9 μM, respectively. These compounds were found to inhibit the mRNA expression of iNOS. The inhibitory activities on the production and mRNA expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 were evaluated.

Bile acid derivatives from a sponge-associated bacterium Psychrobacter sp.

In our search for bioactive metabolites from a marine sponge-associated bacterium Psychrobacter sp., a new bile acid derivative (1), which was assumed to be an artifact, were isolated along with six known (2–7) compounds by bioactivity-guided fractionation. Elucidation of the structure of the new compound was done using a combination of NMR (1H, 13C, HMBC, HSQC, and COSY) and MS spectroscopy. Compound 1 exhibited moderate suppressive effects on both NO and IL-6 production at a concentration of 200 μM (87.3 μg/mL) without significant cytotoxicity against cells. Compounds 2–5 and 7 showed selective inhibitory activity against several human pathogenic bacterial strains at the low concentration of 30 μg/well. In a cytotoxicity evaluation, only compound 7 showed mild cytotoxicity against five human solid tumor cell lines (A-549, SK-OV-3, SK-MEL-2, XF-498, and HCT-15) with ED50 values in the range of 11–14 μg/mL.

Asteropsins B–D, sponge-derived knottins with potential utility as a novel scaffold for oral peptide drugs

BACKGROUND Known linear knottins are unsuitable as scaffolds for oral peptide drug due to their gastrointestinal instability. Herein, a new subclass of knottin peptides from Porifera is structurally described and characterized regarding their potential for oral peptide drug development. METHODS Asteropsins B-D (ASPB, ASPC, and ASPD) were isolated from the marine sponge Asteropus sp. The tertiary structures of ASPB and ASPC were determined by solution NMR spectroscopy and that of ASPD by homology modeling. RESULTS The isolated asteropsins B-D, together with the previously reported asteropsin A (ASPA), compose a new subclass of knottins that share a highly conserved structural framework and remarkable stability against the enzymes in gastrointestinal tract (chymotrypsin, elastase, pepsin, and trypsin) and human plasma. CONCLUSION Asteropsins can be considered as promising peptide scaffolds for oral bioavailability. GENERAL SIGNIFICANCE The structural details of asteropsins provide essential information for the engineering of orally bioavailable peptides.

Solution Structure of a Sponge-Derived Cystine Knot Peptide and Its Notable Stability

A novel cystine knot peptide, asteropsin E (ASPE), was isolated from an Asteropus sp. marine sponge. The primary, secondary, and tertiary structures of ASPE were determined by high-resolution 2D NMR spectroscopy (900 MHz). With the exception of an N-terminal modification, ASPE shares properties with the previously reported asteropsins A-D, that is, the absence of basic residues, a highly acidic nature, conserved structurally important residues (including two cis-prolines), and a highly conserved tertiary structural framework. ASPE was found to be remarkably stable to gastrointestinal tract enzymes (chymotrypsin, elastase, pepsin, and trypsin) and to human plasma.