A chemical investigation of the endophyte Penicillium sp. (strain ZO-R1-1), isolated from roots of the medicinal plant Zingiber officinale, yielded nine new indole diterpenoids (1–9), together with 13 known congeners (10–22). The structures of the new compounds were elucidated by 1D and 2D NMR analysis in combination with HRESIMS data. The absolute configuration of the new natural products 1, 3, and 7 was determined using the TDDFT-ECD approach and confirmed for 1 by single-crystal X-ray determination through anomalous dispersion. The isolated compounds were tested for cytotoxicity against L5178Y, A2780, J82, and HEK-293 cell lines. Compound 1 was the most active metabolite toward L5178Y cells, with an IC50 value of 3.6 μM, and an IC50 against A2780 cells of 8.7 μM. Interestingly, 1 features a new type of indole diterpenoid scaffold with a rare 6/5/6/6/6/6/5 heterocyclic system bearing an aromatic ring C, which is suggested to be important for the cytotoxic activity of this natural product against L5278Y and A2780 cells.

OSMAC approach on endophytic Bulgaria inquinans by addition of a mixture of salts (MgSO4, NaNO3 and NaCl) to solid Czapek medium induced the accumulation of new secondary metabolites.

Sponge-derived fungi have recently attracted attention as an important source of interesting bioactive compounds. Aspergillus nomius NC06 was isolated from the marine sponge Neopetrosia chaliniformis. This fungus was cultured on rice medium and yielded four compounds including three new oxisterigmatocystins, namely, J, K, and L (1, 2, and 3), and one known compound, aspergillicin A (4). Structures of the compounds were elucidated by 1D and 2D NMR spectroscopy and by high-resolution mass spectrometry. The isolated compounds were tested for cytotoxic activity against HT 29 colon cancer cells, where compounds 1, 2, and 4 exhibited IC50 values of 6.28, 15.14, and 1.63 µM, respectively. Under the fluorescence microscope by using a double staining method, HT 29 cells were observed to be viable, apoptotic, and necrotic after treatment with the cytotoxic compounds 1, 2, and 4. The result shows that compounds 1 and 2 were able to induce apoptosis and cell death in HT 29 cells.

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This study aims to find bioactive metabolites from fungus, which was isolated from marine sponge Haliclona fascigera. The fungus was identified molecularly as C. geniculatus WR12. The isolation of the bioactive compound was achieved by column chromatography with step gradient polarity (SGP) method and purification by recrystallization. The structure was determined based on spectroscopic analyses (UV, IR, HR-MS, 1 H and 13 C NMR). The antibacterial activity of the compound was tested against Methicillin-Resistant Staphylococcus Aureus (MRSA) by using the agar diffusion method. The Cytotoxicity of the compound was tested on the cancer cell lines by using the microculture tetrazolium (MTT) assay. The results of this study were obtained a pure compound (1). The compound was identified as radicinin based on 1D and 2D NMR and HRESIMS data. This compound showed cytotoxic activity with IC 50 values of 60.68, 30.89, and 87.89 µg/mL against WiDr, T47D, and Hela cell lines, respectively, but not toxic against Vero cell (IC 50 value of 607.31 µg/mL). Radicinin showed higher cytotoxic activity against T47D cells (IC 50 = 25.01 ppm) compared with doxorubicin (IC 50 = 33.49 ppm). The result of the antibacterial activity of radicinin showed the minimum inhibitory concentration (MIC) of 125 µg/disc against MRSA. Based on these results, it can be concluded that radicinin could be considered as a potential candidate for future anticancer and anti-MRSA drug.

Endophytic fungi isolated from Antidesma bunius leaves were investigated in this study. Six fungal endophytes were identified as Penicillium steckii AAB-01, Nemania bipapillata AAB-02, Xylaria feejeensis AAB-03, Hypomontagnella monticulosa AAB-04, Daldinia eschscholtzii AAB-05, and Phyllosticta capitalensis AAB-06. All of the isolated endophytic fungi were subjected to fermentation on rice media, followed by extraction with ethyl acetate. When tested for antibacterial activity, P. steckii AAB-01 extract showed the most potent inhibition against Staphylococcus aureus ATCC 6538 and Staphylococcus epidermidis ATCC 12228. Toxicity screening employing brine shrimp lethality test (BSLT) revealed potential toxicity of P. steckii AAB-01 and X. feejeensis AAB-03 extracts. Further investigation showed P. steckii AAB-01 extract had the highest inhibition toward MCF-7 cells, while D. eschscholtzii AAB-05 extract revealed the strongest cytotoxicity against 4T1 cells. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis tentatively identified five compounds, where indole acetic acid, O-acetylharmol, and oxindole I were suggested as the major metabolites in P. steckii AAB-01 extract, while 6-hydroxymelatonin and 2-methyl-6pentadecylpyridine were suggested as the major metabolites in D. eschscholtzii AAB-05 extract. This is the first report on LC-MS/MS identification of the main metabolites from bioactive extracts of P. steckii AAB-01 and D. eschscholtzii AAB-05 isolated from the leaves of A. bunius, which might contribute to the antibacterial and cytotoxic properties of the extracts. Thus, a detailed investigation of antibacterial and cytotoxic metabolites from these endophytes merits further studies.

An unusual decahydrofluorene-class alkaloid from Didymella sp. exhibited NFκB inhibitory and antimicrobial activities.

Triple-negative breast cancer (TNBC), representing the most aggressive form of breast cancer with currently no targeted therapy available, is characterized by an inflammatory and hypoxic tumor microenvironment. To date, a broad spectrum of anti-tumor activities has been reported for phenanthroindolizidine alkaloids (PAs), however, their mode of action in TNBC remains elusive. Thus, we investigated six naturally occurring PAs extracted from the plant Tylophora ovata: O-methyltylophorinidine (1) and its five derivatives tylophorinidine (2), tylophoridicine E (3), 2-demethoxytylophorine (4), tylophoridicine D (5), and anhydrodehydrotylophorinidine (6). In comparison to natural (1) and for more-in depth studies, we also utilized a sample of synthetic O-methyltylophorinidine (1s). Our results indicate a remarkably effective blockade of nuclear factor kappa B (NFκB) within 2 h for compounds (1) and (1s) (IC50 = 17.1 ± 2.0 nM and 3.3 ± 0.2 nM) that is different from its effect on cell viability within 24 h (IC50 = 13.6 ± 0.4 nM and 4.2 ± 1 nM). Furthermore, NFκB inhibition data for the additional five analogues indicate a structure–activity relationship (SAR). Mechanistically, NFκB is significantly blocked through the stabilization of its inhibitor protein kappa B alpha (IκBα) under normoxic as well as hypoxic conditions. To better mimic the TNBC microenvironment in vitro, we established a 3D co-culture by combining the human TNBC cell line MDA-MB-231 with primary murine cancer-associated fibroblasts (CAF) and type I collagen. Compound (1) demonstrates superiority against the therapeutic gold standard paclitaxel by diminishing spheroid growth by 40% at 100 nM. The anti-proliferative effect of (1s) is distinct from paclitaxel in that it arrests the cell cycle at the G0/G1 state, thereby mediating a time-dependent delay in cell cycle progression. Furthermore, (1s) inhibited invasion of TNBC monoculture spheroids into a matrigel®-based environment at 10 nM. In conclusion, PAs serve as promising agents with presumably multiple target sites to combat inflammatory and hypoxia-driven cancer, such as TNBC, with a different mode of action than the currently applied chemotherapeutic drugs.