Desheng Liu

Four novel pyranone derivatives were isolated from fungi associated with the marine sponge species Aspergillus versicolor. The planar structures of these compounds were elucidated through comprehensive spectroscopic techniques, including HRESIMS, UV, IR, and 1D and 2D NMR. The absolute configuration of compound 1 was determined via X-ray diffraction, while that of compound 3a was determined using electronic circular dichroism (ECD) spectroscopy. Furthermore, all compounds were evaluated for their cytotoxic activity against human lung carcinoma cells (A549). At 30 μM, only compound 2 exhibited slight cytotoxic activity, with an inhibition rate of (46 ± 3.63)%, compared to doxorubicin (positive control, (86 ± 1.81)%). In DPPH free radical scavenging assays, compound 2 demonstrated a superior capacity than other derivatives, with a scavenging rate of (21.5 ± 3.03)% at 0.6 mg/mL, though still lower than vitamin C ((38.4 ± 2.96)%). Compounds 1, 3a, and 3b exhibited diminished scavenging activities, with rates of (16.1 ± 1.32)%, (13.6 ± 1.60)%, and (15.2 ± 2.79)%, respectively.

Background: In recent decades, spiroketals which features with two rings joined by a spiro atom, have stimulated a great deal of researches for their diverse significant biological activities. Fungi are proved to be key reservoirs of structurally unique chemical skeletons. Up to date, [6,6]-spiroketals from fungal strains are still sporadically reported. Guided by UV information based on HPLC-DAD system, five unreported azaphilone-based [6,6]-spiroketals (1-5), named spirolones A-E, along with one known analogue, pestafolide A (6), were isolated from a productive saline soil derived fungus Penicillium raistrickii.Methods: Their planar structures were solved through a comprehensive set of spectroscopic techniques including UV, IR, HRESIMS and 1D/2D NMR. The absolute configurations were determined by X-ray single-crystal diffractions or the modified Mosher’s method. The misassignment of absolute configuration of pestafolide A was revised by X-ray crystallographic analysis in this study. All the isolated compounds were screened for antibacterial effect against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli based on the microplate approach and the cytotoxicity towards HepG2 and Hep3B cell lines based on MTT assay.Results and discussion: The results suggested that compound 4 displayed some activity against P. aeruginosa and E. coli with MIC values of 35.00 μg/mL and 55.00 μg/mL, with MIC values of the positive control of streptomycin at 12.50 μg/mL and 8.00 μg/mL, respectively. Compound 5 exhibited inhibitory effect against HepG2 cell line with IC50 value of 3.40 μM, and 8.14 μM against Hep3B cell line with doxorubincin as positive control. Compounds 4 and 5 may be capable of contribution for the development of new antibiotics or antitumor agents.

Introduction: Alkaloidal natural products are attractive for their broad spectrum of pharmaceutical bioactivities. In the present work, the highly productive saline soil derived fungus, Penicillium raistrichii, was subjected to the strategy of OSMAC (one strain many compounds) with changes of cultivation status. Then, the work-flow led to the expansion of the alkaloid chemical diversity and subsequently induced the accumulation of four undescribed alkaloids, named raistrimides A–D (1–4), including three β-carbolines (1–3), one 2-quinolinone (4), and one new natural product, 2-quinolinone (5), along with five known alkaloid chemicals (6–10).Methods: A set of NMR techniques including ¹H, ¹³C, HSQC and HMBC, along with other spectroscopic data of UV-Vis, IR and HRESIMS, were introduced to assign the plain structures of compounds 1–10. The absolute configuration of 1–3 were elucidated by means of X-ray crystallography or spectroscopic analyses on optical rotation values and experimental electronic circular dichroism (ECD) data. In addition, it was the first report on the confirmation of structures of 6, 7 and 9 by X-ray crystallography data. The micro-broth dilution method was applied to evaluate antimicrobial effect of all compounds towards Staphylococcus aureus, Escherichia coli, and Candida albicans.Results and discussion: The results indicated compounds 1, 3 and 4 to be bioactive, which may be potential for further development of anti-antimicrobial agents. The finding in this work implied that OSMAC strategy was a powerful and effective tool for promotion of new chemical entities from P. raistrichii.

Secalonic acid F (SAF) is a fungal secondary metabolite exhibited interesting pharmacological effect. In this study, a simple and sensitive ultra-performance liquid chromatography–tandem mass spectrometric (UPLC–MS/MS) method was developed and validated for the determination of SAF in rat plasma. Emodin was selected as the internal standard (IS), and plasma samples were prepared by liquid–liquid extraction with ethyl acetate. Chromatographic separation was operated on an Agilent SB-C₁₈ column, and the mobile phase was a mixture of 0.5% formic acid in water and methanol (V:V = 20:80) at a flow rate of 0.3 mL/min. Detection was carried out with a 6460 triple-quadrupole mass spectrometer using electrospray ionization in the multiple-reaction monitoring mode. The MS/MS ion transitions monitored were m/z 639.3 → 415.4 and 269.0 → 225.1 for SAF and IS, respectively. Results showed the calibration curve of SAF was linear in the range of 2–500 ng·mL⁻¹ with the correlation coefficient > 0.99. The matrix effect, extraction recovery, dilution effect, intraday and inter-day precision and accuracy were all in acceptable limits. The analytes were also stable under different conditions. The validated method was successfully applied to a pharmacokinetic study after oral administration in Sprague-Dawley rats at a dose of 10 mg/kg.

Three new γ-hydroxyl butenolides (1–3), a pair of new enantiomeric spiro-butenolides (4a and 4b), a pair of enantiomeric cyclopentenones (5a new and 5b new natural), and six known compounds (6–11), were isolated from Aspergillus sclerotiorum. Their structures were established by spectroscopic data and electronic circular dichroism (ECD) spectra. Two pairs of enantiomers [(+)/(–)-6c and (+)/(–)-6d] obtained from the reaction of 6 with acetyl chloride (AcCl) confirmed that 6 was a mixture of two pairs of enantiomers. In addition, the X-ray data confirmed that 7 was also a racemate. The new metabolites (1−5) were evaluated for their inhibitory activity against cancer and non-cancer cell lines. As a result, compound 1 exhibited moderate cytotoxicity to HL60 and A549 with IC₅₀ values of 6.5 and 8.9 µM, respectively, and weak potency to HL-7702 with IC₅₀ values of 17.6 µM. Furthermore, compounds 1−9 were screened for their antimicrobial activity using the micro-broth dilution method. MIC values of 200 μg/mL were obtained for compounds 2 and 3 towards Staphylococcus aureus and Escherichia coli, while compound 8 exhibited a MIC of 50 μ/mL towards Candida albicans.

Liver cancer is a very common and significant health problem. Therefore, powerful molecular targeting agents are urgently needed. Previously, we demonstrated that secalonic acid-F (SAF) suppresses the growth of hepatocellular carcinoma (HCC) cells (HepG2), but the other anticancer biological functions and the underlying mechanism of SAF on HCC are unknown. In this study, we found that SAF, which was isolated from a fungal strain in our lab identified as Aspergillus aculeatus, could inhibit the progression of hepatocellular carcinoma by targeting MARCH1, which regulates the PI3K/AKT/β-catenin and antiapoptotic Mcl-1/Bcl-2 signaling cascades. First, we confirmed that SAF reduced the proliferation and colony formation of HCC cell lines (HepG2 and Hep3B), promoted cell apoptosis, and inhibited the cell cycle in HepG2 and Hep3B cells in a dose-dependent manner. In addition, the migration and invasion of HepG2 and Hep3B cells treated with SAF were significantly suppressed. Western blot analysis showed that the level of MARCH1 was downregulated by pretreatment with SAF through the regulation of the PI3K/AKT/β-catenin signaling pathways. Moreover, knockdown of MARCH1 by small interfering RNAs (siRNAs) targeting MARCH1 also suppressed the proliferation, colony formation, migration, and invasion as well as increased the apoptotic rate of HepG2 and Hep3B cells. These data confirmed that the downregulation of MARCH1 could inhibit the progression of hepatocellular carcinoma and that the mechanism may be via PI3K/AKT/β-catenin inactivation as well as the downregulation of the antiapoptotic Mcl-1/Bcl-2. In vivo, the downregulation of MARCH1 by treatment with SAF markedly inhibited tumor growth, suggesting that SAF partly blocks MARCH1 and further regulates the PI3K/AKT/β-catenin and antiapoptosis Mcl-1/Bcl-2 signaling cascade in the HCC nude mouse model. Additionally, the apparent diffusion coefficient (ADC) values, derived from magnetic resonance imaging (MRI), were increased in tumors after SAF treatment in a mouse model. Taken together, our findings suggest that MARCH1 is a potential molecular target for HCC treatment and that SAF is a promising agent targeting MARCH1 to treat liver cancer patients.

Five new (1–5) and two known xanthones (6 and 7), one of the latter (6) obtained for the first time as a natural product, together with three known anthraquinones, questin, penipurdin A, and questinol, were isolated from the coastal saline soil-derived Aspergillus iizukae by application of an OSMAC (one strain many compounds) approach. Their structures were determined by interpretation of nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectroscopy (HRESIMS) data, as well as comparison of these data with those of related known compounds. Antiviral activity of xanthones 1−7 was evaluated through the cytopathic effect (CPE) inhibition assay, and compound 2 exhibited distinctly strong activity towards influenza virus (H1N1), herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) with IC₅₀ values of 44.6, 21.4, and 76.7 μM, respectively, which indicated that it was worth to further investigate it as a potential lead compound. The preliminary structure-activity relationship of the xanthones is discussed.

Three new diastereomers of polyketides (PKs), raistrickiones A−C (1–3), together with two new analogues, raistrickiones D and E (4 and 5), were isolated from a highly productive strain of Penicillium raistrickii, which was subjected to an experimental thermo-change strategy to tap its potential of producing new secondary metabolites. Metabolites 1 and 2 existed in a diastereomeric mixture in the crystal packing according to the X-ray data, and were laboriously separated by semi-preparative HPLC on a chiral column. The structures of 1–5 were determined on the basis of the detailed analyses of the spectroscopic data (UV, IR, HRESIMS, 1D, and 2D NMR), single-crystal X-ray diffractions, and comparison of the experimental and calculated electronic circular dichroism spectra. Compounds 1–5 represented the first case of 3,5-dihydroxy-4-methylbenzoyl derivatives of natural products. Compounds 1–5 exhibited moderate radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH).

Secalonic acid- F inhibited cell growth more effectively than 5-fluorouracil on hepatocellular carcinoma in vitro and in vivo