Cai-Juan Zheng

Antibacterial Bisabolane-Type Sesquiterpenoids from the Sponge-Derived Fungus Aspergillus sp.

Four new bisabolane-type sesquiterpenoids, aspergiterpenoid A (1), (−)-sydonol (2), (−)-sydonic acid (3), and (−)-5-(hydroxymethyl)-2-(2′,6′,6′-trimethyltetrahydro-2H- pyran-2-yl)phenol (4) together with one known fungal metabolite (5) were isolated from the fermentation broth of a marine-derived fungus Aspergillus sp., which was isolated from the sponge Xestospongia testudinaria collected from the South China Sea. Four of them (1–4) are optically active compounds. Their structures and absolute configurations were elucidated by using NMR spectroscopic techniques and mass spectrometric analysis, and by comparing their optical rotations with those related known analogues. Compounds 1–5 showed selective antibacterial activity against eight bacterial strains with the MIC (minimum inhibiting concentrations) values between 1.25 and 20.0 µM. The cytotoxic, antifouling, and acetylcholinesterase inhibitory activities of these compounds were also examined.

Antibacterial Anthraquinone Derivatives from a Sea Anemone-Derived Fungus Nigrospora sp.

Chemical investigation of a marine-derived fungus Nigrospora sp., isolated from an unidentified sea anemone, yielded two new hydroanthraquinone analogues, 4a-epi-9α-methoxydihydrodeoxybostrycin (1) and 10-deoxybostrycin (2), together with seven known anthraquinone derivatives (3-9). The structures of the two new compounds were established through extensive NMR spectroscopy as well as a single-crystal X-ray diffraction analysis using Cu Kα radiation. The antibacterial activities of compounds 1-9 and 10 acetyl derivatives (6a, 7a, 8a-8g, 9a) were evaluated in vitro. Compound 6a, the acetylated derivative of 6, exhibited promising activity against Bacillus cereus with an MIC value of 48.8 nM, which was stronger than that of the positive control ciprofloxacin (MIC = 1250 nM). Analysis of the antibacterial screening data for the metabolites and their acetyl derivatives revealed the key structural features required for this activity.

Bioactive Phenylalanine Derivatives and Cytochalasins from the Soft Coral-Derived Fungus, Aspergillus elegans

One new phenylalanine derivative 4′-OMe-asperphenamate (1), along with one known phenylalanine derivative (2) and two new cytochalasins, aspochalasin A1 (3) and cytochalasin Z24 (4), as well as eight known cytochalasin analogues (5–12) were isolated from the fermentation broth of Aspergillus elegans ZJ-2008010, a fungus obtained from a soft coral Sarcophyton sp. collected from the South China Sea. Their structures and the relative configurations were elucidated using comprehensive spectroscopic methods. The absolute configuration of 1 was determined by chemical synthesis and Marfey’s method. All isolated metabolites (1–12) were evaluated for their antifouling and antibacterial activities. Cytochalasins 5, 6, 8 and 9 showed strong antifouling activity against the larval settlement of the barnacle Balanus amphitrite, with the EC50 values ranging from 6.2 to 37 μM. This is the first report of antifouling activity for this class of metabolites. Additionally, 8 exhibited a broad spectrum of antibacterial activity, especially against four pathogenic bacteria Staphylococcus albus, S. aureus, Escherichia coli and Bacillus cereus.

A new anthraquinone derivative from the marine endophytic fungus Fusarium sp. (No. b77).

A new anthraquinone compound, 5-acetyl-2-methoxy-1,4,6-trihydroxy-anthraquinone (1), together with four known naphthoquinones (2–5), were isolated from the culture of the mangrove fungus (No. b77). All the isolated compounds (1–5) and the acetyl derivative (1a) were established by comprehensive analysis of the spectral data, especially 1D- and 2D-NMR (HMQC and HMBC) spectra. In the primary bioassays, compound 3 showed strong inhibitory effects on the growth of hepG2 and hep2 cells, with IC50 values of 1.0 and 2.5 µg mL−1, respectively.

Diversity and antibacterial activities of fungi derived from the Gorgonian Echinogorgia rebekka from the South China Sea.

The diversity of symbiotic fungi associated with the gorgonian coral Echinogorgia rebekka from the Weizhou coral reef in the South China Sea was investigated. Combined with morphologic traits, ITS-rDNA sequences revealed 18 fungal strains from this gorgonian. All of the 18 fungi belonged to the phylum Ascomycota and were distributed among seven genera in five orders: Eurotiales (Aspergillus and Penicillium), Pleosporales (Alternaria), Capnodiales (Cladosporium), Trichosphaeriales (Nigrospora) and Hypocreales (Hypocrea and Nectria). Antibacterial activities of these fungal strains were investigated with five pathogenic bacteria. All of the 18 fungal strains displayed different levels of antibacterial activities, most of which exhibited moderate to high antibacterial activities to the Gram-positive pathogens Staphylococcus aureus and Micrococcus tetragenus, and showed relatively low bioactivities to other three pathogenic bacteria. Several fungal strains in the genera Penicillium and Cladosporium with strong antibacterial activities provide potential for further research on isolation of bioactive secondary metabolites.

Secondary metabolites from green algae Ulva pertusa

0009-3130/10/4605-0828 2010 Springer Science+Business Media, Inc. 1) Key Laboratory of Marine Drugs, Ministry of Education, the School of Medicine and Pharmacy, Ocean University of P. R. China, Qingdao 266003, China, e-mail: changyun@ouc.edu.cn; 2) School of Medicine, Qingdao University, Qingdao 266071, P. R. China. Published in Khimiya Prirodnykh Soedinenii, No. 5, pp. 699–701, September–October, 2010. Original article submitted April 15, 2009. Chemistry of Natural Compounds, Vol. 46, No. 5, 2010

Chemical constituents from the fruits of Ligustrum lucidum

One new δ-valerolactone (1) and one new natural phenolic glycoside 2, together with four known compounds 3–6, were isolated from the fruits of Ligustrum lucidum. Their structures were elucidated on the basis of spectral data. The chemical transformation from 2 to 3 was observed. The immunomodulatory activities of the compounds were also evaluated.

Subergorgiaols A-L, 9,10-secosteroids from the South China Sea gorgonian Subergorgia rubra.

Twelve new 9,10-secosteroids designated as subergorgiaols A-L (1-12), along with four known analogues (13-16), were isolated from the gorgonian Subergorgia rubra collected from the South China Sea. Their planar structures and the relative configurations were elucidated by comprehensive spectroscopic methods including NOESY spectra. The absolute configuration of 1 was established by a dimolybdenum tetraacetate [Mo2(AcO)4] induced circular dichroism (ICD) procedure and the modified Moshers method. Compounds 1-12 represent the first series of 9,10-secosteroids characterized with a hydroxy group at C-8, which are 8-OH derivatives of astrogorgiadiols/calicoferols. Compound 4 exhibited cytotoxicity against the cervical carcinoma cell line (CaSki) with an IC50 value of 2.4 μM, and 6 showed toxicity toward brine shrimp Artemia salina with an LC50 value of 2.0 μM.

Bioactive Perylene Derivatives from a Soft Coral-Derived Fungus Alternaria sp. (ZJ-2008017)

Marine-derived fungi have proved to be a promising source of structurally novel and biologically active secondary metabolites that have become interesting and significant resources for drug discovery [1, 2]. Perylene derivatives have been isolated from the marine-derived fungi of the genera of Alternaria and Stemphylium [3, 4]. They are of ten were found to have a partially reduced perylene quinone skeleton, and such perylene derivatives sometimes show a variety of phytotoxins and mutagenic activities [4]. As part of our ongoing investigation into new natural products, a series of antibacterial, antifouling, and cytotoxic compounds have been isolated from marine-derived fungi from the South China Sea [5–11]. Chemically-induced teratogenicity is preventable with proactive reproductive safety evaluations. The developing zebrafish (Daniorerio) is an in vivo developmental model with a number of advantages over in vitro systems and provides a simple, inexpensive, and rapid assay to screen for teratogenicity [10, 11]. From a zebrafish embryo teratogenicity assay, five perylene derivatives were isolated from the EtOAc extract of the marine-derived fungus Alternaria sp. ZJ-2008017. The fungus was isolated from a soft coral, Sarcophyton sp., collected from Weizhou Island in the South China Sea. The isolated structures were identified as 7-epi-8-hydroxyaltertoxin I (1) [4], stemphytriol (2) [14], altertoxin I (3) [15], stemphyltoxin II (4) [16], and stemphyperylenol (5) [17] on the basis of their spectroscopic data and by comparison with those previously reported in the literature. All compounds were isolated for the first time from the soft coral-derived fungi. Compounds 1–5 represent a class of perylene derivatives with a partially reduced perylene quinone skeleton. Their biosynthesis occurs probably via a phenol coupling of two pentaketide-derived moieties, followed by reduction and hydroxylation or epoxidation in different positions [15, 16, 18, 19]. To the best of our knowledge, most of the perylenequinones appear to derive from a head-to-head linkage such as 1–4; however, 5 seems to be a head-to-tail linkage of these moieties. Previous research revealed that some of these derivatives are phytotoxins and mutagens [4]. In our study, the zebrafish embryo teratogenicity and antifouling activity were evaluated for perylene derivatives for the first time. Compound 3 showed strong zebrafish embryo teratogenicity on Daniorerio with LC50 value of 4.54 g/mL on lethality of zebrafish embryo, and with EC50 values of 4.21 and 4.47 g/mL on inhibiting the incubation and deformity of zebrafish embryo, respectively. Compound 3 also exhibited potent antifouling activity against the barnacle Balanusamphitrite with an IC50 value of 0.27 g/mL, suggesting that 3 might be useful as a potential antifouling agent.

Merosesquiterpenoids and Ten-Membered Macrolides from a Soft Coral-Derived Lophiostoma sp. Fungus

One new merosesquiterpenoid, craterellin D (1), along with one known analog, craterellin A (2), and five known ten‐membered macrolides, 3–7, were isolated from a soft coral‐derived Lophiostoma sp. fungus. The absolute configuration of 1 was established based on biogenetic consideration with the co‐isolated analog 2, whose configuration was determined by modified Moshers method and single‐crystal X‐ray diffraction analysis using CuKα radiation. The absolute configuration of 3 was determined by X‐ray diffraction analysis using CuKα radiation. Compounds 2 and 3 showed antibacterial activities against Bacillus cereus with a MIC value of 3.12 μM.