Isolation and Characterization of Anti-Inflammatory Sorbicillinoids from the Mangrove-Derived Fungus Penicillium sp. DM815.

Marine derived fungus has gained increasing ground in the discovery of novel lead compounds with potent biological activities including anti-inflammation. Here, we first report the characterization of one new sorbicillinoid (1) and fourteen known compounds (2-15) from the ethyl acetate (AcOEt) extract of a cultured mangrove derived fungus Penicillium sp. DM815 by UV, IR, HR ESI-Q-TOF MS, and NMR spectra. We then evaluated the anti-inflammatory effects of eleven sorbicillinoids (1-11) using cultured macrophage RAW264.7 cells. The results show that compound 9, and to a lesser degree compound 5, significantly inhibited the Gram-negative bacteria lipopolysaccharide (LPS)-induced upregulation of the inducible nitric oxide synthase (iNOS). Consistently, compounds 5 and 9 significantly reduced the level of nitric oxide (NO), the product of iNOS, induced by LPS. We further show that these two compounds dose-dependently inhibited LPS-triggered iNOS expression and NO production, but had no effect on proliferation of RAW264.7 cells in the presence of LPS. In conclusion, our study identifies novel and known sorbicillinoids as potent anti-inflammatory agents, holding the promise of developing novel anti-inflammation treatment in the future.

New pyrones and their analogs from the marine mangrove-derived Aspergillus sp. DM94 with antibacterial activity against Helicobacter pylori.

Marine fungi are well known for their ability to produce a multitude of natural products and have been proved to be a particularly rich source of drug leads. Here, 20 pyrones and their analogs (1-20), including two new compounds (1 and 6), were obtained from a marine-derived fungus strain of Aspergillus sp. DM94. Their structures were determined by analyses of UV, IR, HR-ESI-MS, and NMR data. The ability to inhibit Helicobacter pylori in vitro was assessed for these isolated compounds. Results showed that the bis-naphtho-γ-pyrones exhibited potent antibacterial activity against both the standard and multidrug-resistant H. pylori strains. Structure-activity relationship (SAR) analysis suggested that the bis-naphtho[2,3-b]pyrones showed better anti-H. pylori activity than a hybrid of naphtho[2,3-b]pyrone and naphtho[1,2-b]pyrone. In addition, the free hydroxyl group of the C-8 position in the lower unit is vital for its anti-H. pylori activity. Importantly, compound 18 showed a synergistic effect in combination with amoxicillin, clarithromycin, or metronidazole, suggesting its potential use to overcome antibiotic resistance of H. pylori. This study shed light on the discovery of new anti-H. pylori agents. KEY POINTS: • New pyrones discovered from a marine-derived fungus Aspergillus sp. DM94. • Bis-naphtho-γ-pyrones showed potent anti-H. pylori activity. • The anti-H. pylori SAR analysis of bis-naphtho-γ-pyrones was discussed. • Bis-naphtho-γ-pyrone 18 showed synergistic effect with clinical antibiotics.

Two new bioactive steroids from a mangrove-derived fungus Aspergillus sp.

Two unusual naturally Diels-Alder additive steroids, ergosterdiacids A and B (1 and 2), constructing a 6/6/6/6/5 pentacyclic steroidal system, together with three known compounds (3-5) were obtained from the mangrove-derived fungus Aspergillus sp. Their structures were elucidated based on the comprehensive spectroscopic analysis, including 1D, 2D NMR and HRESIMS, as well as the quantum chemical ECD calculations. The plausible biosynthetic pathways of 1 and 2 were discussed. In the bioactivity assays, 1 and 2 exhibited potential in vitro inhibition activity against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with an IC50 value of 15.1 and 30.1 µM, respectively. The inhibitory kinetic experiments indicated that both of them acted via a noncompetitive inhibition mechanism. Moreover, 1 and 2 showed strong in vitro anti-inflammatory effects by suppressing the NO production at 4.5 and 3.6 µM, respectively.