An anti-HBV anthraquinone from aciduric fungus Penicillium sp. OUCMDZ-4736 under low pH stress

Abstract

To obtain new bioactive natural products, the effect of acidic stress on the metabolites of an aciduric fungus was investigated. This fungus, Penicillium sp. OUCMDZ-4736, which was isolated from the sediment around roots of mangrove (Acanthus ilicifolius), produced different compounds and higher yields under pH 2.5 than under neutral conditions. Using spectroscopic analyses and calculations, three new anthraquinone derivatives (1-3) were isolated and identified from the acidic fermentation broth (pH 2.5) of OUCMDZ-4736. Compound 1 showed much stronger anti-hepatitis B virus activity than that of the positive control, lamivudine, strongly inhibiting HBsAg and HBeAg secretion from HepG2.2.15 cells. These results show that extremophiles are a valuable resource of bioactive compounds, and that pH regulation is an effective strategy to induce metabolite production in aciduric fungi.

The anti‐hepatitis B virus therapeutic potential of anthraquinones derived from Aloe vera

“…Taken together, our three tested AV‐derived anthraquinones (10 μg/ml) show a high anti‐HBV activity (60–80%) almost comparable with lamivudine (2.0 μM). This is in contrast to the recently reported lower anti‐HBV activities (17–35%) of Penicillium‐ derived anthraquinone derivatives and Lamivivudine or 3TC (Jin et al, ).…”

“…In addition to the known antiviral natural anthraquinones (Andersen et al, ; Cohen et al, ; Sydiskis et al, ), an acidiuric Penicillium –derived new anthraquinones at nontoxic dose of 20 μM are very recently reported to inhibit HBsAg and HBeAg secretions in HepG2.2.15 cells (Jin et al, ). Notably, although some anthraquinones isolated from Morinda umbellata are reported for cytotoxic or antiproliferative activities in cultured HepG2 cells (Chiou, Hsu, & Lin, ), Rheum palmatum –derived aloe‐emodin is shown to have in vitro anticancer property (Huang, Lu, Shen, Chung, & Ong, ).…”

“…Very recently, some new anthraquinones isolated from Penicillium sp. are reported to inhibit HBV antigens (HBsAg and HBeAg) expressions in cultured HepG2.2.15 cells (Jin et al, ). However, as compared with other viruses, the anti‐HBV efficacy of AV or its phytoconstituents still remains unexplored.…”

Polyketides From the Endophytic Fungus Cladosporium sp. Isolated From the Mangrove Plant Excoecaria agallocha

“…Calculations for ECD and [α] D were performed in HyperChem 7.5 and Gaussian 03 (Frisch et al, 2004 ; Chen et al, 2016 ; Jin et al, 2018 ). Karplus formula was used to compute the coupling constant ( 3 J ) from the proton-proton torsion angle (Haasnoot et al, 1980 ).…”

Recent progresses in marine microbial-derived antiviral natural products

“…Two anthraquinone derivatives, (‒)-2′ R -1-hydroxyisorhodoptilometrin ( 13 ) and methyl 6,8-dihydroxy-3-methyl-9-oxo-9 H -xanthene-1-carboxylate ( 14 ) (Jin et al 2017 ) (Fig. 2 ) were isolated from the acidic fermentation broth (pH 2.5) of Penicillium sp.…”