Search

The Wnt/β-catenin signaling pathway is an evolutionarily conserved signaling cascade involved in a broad range of biological roles. Dysregulation of the Wnt/β-catenin pathway is implicated in congenital malformations and various kinds of cancers. We discovered a novel Wnt/β-catenin inhibitor, talaverrucin A ( 1 ), featuring an unprecedented 6/6/6/5/5/5/6 fused ring system, from an Antarctica sponge-derived fungus Talaromyces sp. HDN151403. Talaverrucin A exhibits inhibitory activity on the Wnt/β-catenin pathway in both zebrafish embryos in vivo and cultured mammalian cells in vitro , providing a naturally inspired small molecule therapeutic lead to target the Wnt/β-catenin pathway.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplastic diseases of the pancreas with fatal proliferation and metastasis and no medicine available for treatment. From an Antarctica sponge-derived fungus, Aspergillus insulicola HDN151418, four new nitrobenzoyl sesquiterpenoids, namely, insulicolides D-G ( 1 - 4 ), were isolated. Compounds 3 and 4 exhibited selective inhibition against human PDAC cell lines. Further studies indicated that compound 4 could significantly suppress cell proliferation to induce apoptosis and blocked migration and invasion of PDAC cells. Compound 4 could also avoid resistance and improved the therapeutic effect of the chemotherapy drug gemcitabine. A preliminary mechanism study showed that compound 4 can significantly inhibit the expression of EGFR and XIAP in PDAC cells. Altogether, 4 is a potential lead compound for anti-PDAC drug research.

Six new nonadride derivatives, named talarodrides A-F ( 1 - 6 ), were isolated from the Antarctic sponge-derived fungus Talaromyces sp. HDN1820200. All structures including the absolute configurations were deduced by extensive spectroscopic analysis and computational ECD calculations. Compounds 1 - 4 share a rare caged bicyclo[4.3.1]-deca-1,6-diene with a bridgehead olefin and maleic anhydride core skeleton, while compounds 5 and 6 possess the first case of a naturally occurring 5/7/6 methanocyclonona[ c ]furan skeleton. Talarodride A ( 1 ) and talarodride B ( 2 ) showed selective inhibitory effects against Proteus mirabilis and Vibrio parahemolyticus with MICs of 3.13-12.5 μM.

Four new anthraquinone derivatives, namely saliniquinones G-I ( 1 - 3 ) and heraclemycin E ( 4 ), were obtained from the Antarctic marine-derived actinomycete Nocardiopsis aegyptia HDN19-252, guided by the Global Natural Products Social (GNPS) molecular networking platform. Their structures, including absolute configurations, were elucidated by extensive NMR, MS, and ECD analyses. Compounds 1 and 2 showed promising inhibitory activity against six tested bacterial strains, including methicillin-resistant coagulase-negative staphylococci (MRCNS), with MIC values ranging from 3.1 to 12.5 μM.

Three new aspochracin-type cyclic tripeptides, sclerotiotides M-O ( 1 - 3 ), together with three known analogues, sclerotiotide L ( 4 ), sclerotiotide F ( 5 ), and sclerotiotide B ( 6 ), were obtained from the ethyl acetate extract of the fungus Aspergillus insulicola HDN151418, which was isolated from an unidentified Antarctica sponge. Spectroscopic and chemical approaches were used to elucidate their structures. The absolute configuration of the side chain in compound 4 was elucidated for the first time. Compounds 1 and 2 showed broad antimicrobial activity against a panel of pathogenic strains, including Bacillus cereus , Proteus species , Mycobacterium phlei , Bacillus subtilis , Vibrio parahemolyticus , Edwardsiella tarda , MRCNS, and MRSA, with MIC values ranging from 1.56 to 25.0 µM.

Three new polyketides, ketidocillinones A-C ( 1 - 3 ), were discovered from the extract of an Antarctica sponge-derived fungus Penicillium sp. HDN151272. All the structures were deduced by spectroscopic data, including NMR and HRESIMS. The absolute configuration of compound 3 was established by using ECD calculation. Compounds 1 - 3 can be slowly oxidized to quinone form when exposed to air. Ketidocillinones B and C ( 2 and 3 ) exhibited potent antibacterial activity against Pseudomonas aeurigenosa , Mycobacterium phlei, and MRCNS (methicillin-resistant coagulase-negative staphylococci ) with MIC values ranging from 1.56 to 25.00 µg/mL., Competing Interests: The authors declare no conflict of interest.