Lucidumones B-H, racemic meroterpenoids that inhibit tumor cell migration from Ganoderma lucidum.

Seven new meroterpenoids, lucidumones B-H (1 and 3-8), along with one known meroterpenoid (2), were isolated from the fruiting bodies of Ganoderma lucidum. The structures of the new compounds were assigned by spectroscopic and computational methods. All the isolated compounds were tested for their inhibition on human cancer cell migration. It was found that compounds (-)-1, (+)-2, (-)-4, (+)-6, and (+)-8 could significantly inhibit cell migration in KYSE30 cell line. Further examination disclosed that cell migration inhibition of (+)-6 and (+)-8 might be related with downregulation of N-cadherin.

Acute and subacute inhalation toxicity assessment of WS-23 in Sprague-Dawley rats.

2-isopropyl-N,2,3-trimethylbutyramide (WS-23) is a well-known artificial synthesis cooling agent widely used in foods, medicines, and tobaccos. As a commonly cooling agent in e-cigarette liquids, WS-23 has led to concerns about the inhalation toxicity with the prosperous of e-cigarettes in recent years. Thus, the aim of this study is to assess the acute and subacute inhalation toxicity of WS-23 in Sprague-Dawley (SD) rats according to the Organization for Economic Cooperation and Development (OECD) guidelines. In the acute toxicity study, there was no mortality and behavioral signs of toxicity at the limit test dose level (340.0 mg/m3 ) in the exposure period and the following 14-day observation period. In the subacute inhalation toxicity study, there was no significant difference observed in the body weights, feed consumption, and relative organ weights. Haematological, serum biochemical, urine, and bronchoalveolar lavage fluid (BALF) analysis revealed the non-adverse effects after 28-day repeated WS-23 inhalation (342.85 mg/m3 ), accompanied by slight changes in few parameters which returned to normal during the 28-day recovery period. The histopathologic examination also did not show any differences in vital organs. In conclusion, the maximum tolerated dose for WS-23 acute inhalation is not less than 340.0 mg/m3 , and the No Observed Adverse Effect Level (NOAEL) of WS-23 subacute inhalation was determined to be over 342.85 mg/m3 .

Ganocapenoids A-D: Four new aromatic meroterpenoids from Ganoderma capense.

Four new aromatic meroterpenoids, ganocapenoids A-D (1-4), together with twelve known analogues (5-16) were isolated from the fruiting bodies of Ganoderma capense. The structures of new compounds were determined through spectroscopic methods including 1D and 2D NMR and MS analyses. Their absolute configurations were assigned by ECD calculations and specific rotation comparison. The biological activities of these substances toward regulation of lipid metabolism, neurite outgrowth-promoting activity, and AchE inhibition were assessed. Compound 15 was found to be able to block lipid accumulation at a concentration of 20 µM, and compounds 4a, 4b, and 11 show moderate neurite outgrowth-promoting activity at 10 µM, while compounds 3, 6, 11, and 13 exhibit potent AchE inhibition with the IC50 values of 28.6 ±â€¯1.9, 18.7 ±â€¯1.6, 8.2 ±â€¯0.2, 26.0 ±â€¯2.9 µM, respectively.

Salicylic acid derivatives and phenylspirodrimanes from the sponge-associated fungus Hansfordia sinuosae.

Three new salicylic acid derivatives (1-3) and a known one, 6-(3'-hydroxypropyl)-2-hydroxybenzoic acid (4), together with seven known phenylspirodrimanes (5-11), were isolated from the sponge-associated fungus Hansfordia sinuosae, collected from the South China Sea. HRESIMS, FT-IR Spectroscopy, and NMR techniques including COSY, HSQC, and HMBC were used to elucidate the structures of these compounds. The inhibitory effects of the isolated compounds (1-11) against HIV-1 virus were evaluated, and most of the phenylspirodrimanes (5, 8-11) showed varying degrees of anti-HIV activity.

Mini-Review: Antifouling Natural Products from Marine Microorganisms and Their Synthetic Analogs.

Biofouling causes huge economic loss and generates serious ecological issues worldwide. Marine coatings incorporated with antifouling (AF) compounds are the most common practices to prevent biofouling. With a ban of organotins and an increase in the restrictions regarding the use of other AF alternatives, exploring effective and environmentally friendly AF compounds has become an urgent demand for marine coating industries. Marine microorganisms, which have the largest biodiversity, represent a rich and important source of bioactive compounds and have many medical and industrial applications. This review summarizes 89 natural products from marine microorganisms and 13 of their synthetic analogs with AF EC50 values ≤ 25 µg/mL from 1995 (the first report about marine microorganism-derived AF compounds) to April 2017. Some compounds with the EC50 values < 5 µg/mL and LC50/EC50 ratios > 50 are highlighted as potential AF compounds, and the preliminary analysis of structure-relationship (SAR) of these compounds is also discussed briefly. In the last part, current challenges and future research perspectives are proposed based on opinions from many previous reviews. To provide clear guidance for the readers, the AF compounds from microorganisms and their synthetic analogs in this review are categorized into ten types, including fatty acids, lactones, terpenes, steroids, benzenoids, phenyl ethers, polyketides, alkaloids, nucleosides and peptides. In addition to the major AF compounds which targets macro-foulers, this review also includes compounds with antibiofilm activity since micro-foulers also contribute significantly to the biofouling communities.

Biological and Chemical Diversity of Bacteria Associated with a Marine Flatworm.

The aim of this research is to explore the biological and chemical diversity of bacteria associated with a marine flatworm Paraplanocera sp., and to discover the bioactive metabolites from culturable strains. A total of 141 strains of bacteria including 45 strains of actinomycetes and 96 strains of other bacteria were isolated, identified and fermented on a small scale. Bioactive screening (antibacterial and cytotoxic activities) and chemical screening (ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)) yielded several target bacterial strains. Among these strains, the ethyl acetate (EA) crude extract of Streptomyces sp. XY-FW47 fermentation broth showed strong antibacterial activity against methicillin-resistant Staphylococcus aureus ATCC43300 (MRSA ATCC43300) and potent cytotoxic effects on HeLa cells. The UPLC-MS spectral analysis of the crude extract indicated that the strain XY-FW47 could produce a series of geldanamycins (GMs). One new geldanamycin (GM) analog, 4,5-dihydro-17-O-demethylgeldanamycin (1), and three known GMs (2-4) were obtained. All of these compounds were tested for antibacterial, cytotoxic, and antifungal activities, yet only GM (3) showed potent cytotoxic (HeLa cells, EC50 = 1.12 µg/mL) and antifungal (Setosphaeria turcica MIC = 2.40 µg/mL) activities. Their structure-activity relationship (SAR) was also preliminarily discussed in this study.

A new prenylated flavone from Pleione bulbocodioides.

A new prenylated flavone, 3,5,7,3'-tetrahydroxy-8,4'-dimethoxy-6-(3-methylbut-2- enyl)flavone (1), together with three known flavone derivatives (2-4), two known dihydrophenanthrenes (5-6), two known lignin derivatives (7-8), and three known phenolic glycoside compounds (9-11) were isolated from the n-BuOH extract of Pleione bulbocodioides. High-resolution electrospray ionization mass spectroscopy (HRESIMS), FTIR spectroscopy, and NMR techniques were used to elucidate the structures of these compounds. Biological investigations showed that compound 5, 4,7-dihydroxy-2-methoxy-9,10-dihydrophenanthrene, exhibited potent anti-inflammatory activity on LPS-stimulated NO production in BV-2 microglial cells, with IC50 value of 5.44 µM.

Cytotoxic scalarane sesterterpenoids from the South China Sea sponge Carteriospongia foliascens.

Eleven new scalarane sesterterpenoids, including three 20,24-bishomo-25-norscalaranes, carteriofenones A­C (1­3), and eight 20,24-bishomoscalaranes, carteriofenones D­K (4­11), along with two known analogues (12 and 13), were obtained from the marine sponge Carteriospongia foliascens collected from the South China Sea. Their planar structures and relative configurations were elucidated by extensive NMR spectroscopic data. The absolute configuration of 3 was determined using the modified Mosher's method on its hydrolysis product. Scalarane sesterterpenoids with 4-methylpentanate or pentanoate substituents at the 12-position (1­8) were reported for the first time. Carteriofenones E­H (5­8) represented rare naturally occurring scalarane sesterterpenoids with a cyclobutane ring. Compound 4 showed cytotoxicity against the mouse lymphocytic leukemia cell line (P388) with an IC50 value of 0.96 µM.

Chemical analysis of selected harmful and potentially harmful constituents and in vitro toxicological evaluation of leading flavoured e-cigarette aerosols in the Chinese market.

Use of electronic cigarettes (e-cigarettes) has increased significantly over the past decade due to consumer perception that these products represent a less risky alternative to combustible cigarettes. E-liquids generally contain a simple mix of vegetable glycerin, propylene glycerol, nicotine, organic acids, and flavourings. Regulators require that harmful and potentially harmful constituents (HPHCs) that might cause harm to the consumer must be monitored in the aerosol generated by e-cigarettes and in cigarette smoke (CS). To quantify HPHCs in aerosols from commercial flavoured e-cigarettes in Chinese market, this study has systematically compared levels of HPHCs, including eight carbonyls, five volatile organic compounds, four tobacco-specific nitrosamines, 16 polycyclic aromatic hydrocarbons, and seven heavy metals, in the aerosols of four market-leading flavoured e-cigarettes and mainstream CS, alongside in vitro cytotoxicity and mutagenicity assays. The vast majority of HPHCs were either undetected or significantly lower in the e-cigarette aerosols than in commercial CS or reference CS (3R4F). Where HPHCs were detected, there were small variations among the different flavoured e-cigarettes. In the neutral red uptake and Ames assays, aqueous extracts of the e-cigarette aerosols did not induce obvious cytotoxicity or mutagenicity, whereas CS aqueous extract showed dose-related cytotoxicity and mutagenicity. Collectively, these results indicate that use of e-cigarettes might potentially lead to a significant reduction in exposure to harmful substances, with fewer cytotoxic and mutagenic effects, as compared with conventional smoking. Further studies based on human puffing conditions and longer evaluation periods will be needed to substantiate this potential.

Zizhines G-O, AchE inhibitory meroterpenoids from Ganoderma sinensis.

Zizhines G-O (1-9), nine new meroterpenoids, and seven known analogs (10-16) were isolated from the dried fruiting bodies of Ganoderma sinensis. Their structures were identified by using spectroscopic data and CD curve comparison. The inhibitory activities of the selected new meroterpenoids toward AchE were assessed in vitro. Compounds 1-6 and 10-14 were found to exhibit AchE inhibitory activities at the concentration of 50 µM.

Renoprotective phenolic meroterpenoids from the mushroom Ganoderma cochlear.

Twelve previously undescribed phenolic meroterpenoids, cochlearols N-Y, along with two known analogs, ganocochlearins B and C, were isolated from the fruiting bodies of Ganoderma cochlear. Most of these substances were isolated as racemic mixtures. The structures of cochlearols N-Y were assigned based upon spectroscopic data and theoretical calculations. The renoprotective activities of these compounds were evaluated using normal and diseased rat renal interstitial fibroblast cells (NRK-49F). The results show that ganocochlearins S, U, X and Y display potent inhibitory activities against fibronectin overproduction in TGF-ß1-induced NRK-49F cells.

Antifungal coumarins and lignans from Artemisia annua.

Two new coumarins (1 and 2), two new lignans (3 and 4), one new phloroglucinol derivative (5), together with eleven known compounds, were isolated from Artemisia annua. Their structures were identified by spectroscopic methods with 1 to be secured by X-ray diffraction. Antifungal activities of the isolates against Fusarium oxysporum, Fusarium solani, and Cylindrocarpon destrutans were evaluated. It was found that compound 1 could inhibit all the fungal strains with respective MIC values of 18.75, and 25.00 µg/mL. In contrast, compounds 4, 5, 7, and 8 are active toward C. destrutans and 14 displays inhibitory property toward F. solani.

Renoprotective meroterpenoids from the fungus Ganoderma cochlear.

Nine multifarious new meroterpenoids, cochlearols E-M (1-9), along with seven known meroterpenoids 10-16, were isolated from the fruiting bodies of Ganoderma cochlear. Racemic 1, 6-8, 10 and 13 were separated by chiral HPLC. The structures were elucidated based on detailed spectroscopic analyses (HRESIMS, 1D/2D-NMR) and calculated electronic circular dichroism (ECD). Their biological activities against renal fibrosis were evaluated by using rat normal and diseased renal interstitial fibroblast cells (NRK49F). The results show that compounds 7a, 7b, and 10a exhibit potent proliferation inhibition in TGF-ß1-induced NRK-49F cells.

Antioxidant xanthones and anthraquinones isolated from a marine-derived fungus Aspergillus versicolor.

Chemical examination of an EtOAc extract of cultured Aspergillus versicolor fungus from deep-sea sediments resulted in the isolation of four xanthones, eight anthraquinones and five alkaloids, including a new xanthone, oxisterigmatocystin D (1) and a new alkaloid, aspergillusine A (13). High resolution electron impact mass spectrometry (HR-EI-MS), FT-IR spectroscopy, and NMR techniques were used to elucidate the structures of these compounds, and the absolute configuration of compound 1 was established by its NMR features and coupling constant. Furthermore, the biosynthesis pathway of these xanthones and anthraquinones were deduced, and their antioxidant activity and cytotoxicity in human cancer cell lines (HTC-8, Bel-7420, BGC-823, A549, and A2780) were evaluated. The trolox equivalent antioxidant capacity (TEAC) assay indicated most of the xanthones and anthraquinones possessing moderate antioxidant activities. The Nrf2-dependent luciferase reporter gene assay revealed that compounds 6, 7, 9, and 12 potentially activated the expression of Nrf2-regulated gene. In addition, compounds 5 and 11 showed weak cytotoxicity on A549 with the IC50 values of 25.97 and 25.60 µmol·L-1, respectively.

Nitrogen-containing bibenzyls from Pleione bulbocodioides: absolute configurations and biological activities.

Four new pyrrolidone substituted bibenzyls, dusuanlansins A-D (1-4) were isolated from the pseudo bulbs of Pleione bulbocodioides, along with 19 known compounds (5-23). Compounds 1-4 are two pairs of epimers of pyrrolidone substituted bibenzyls, which were separated successfully by a Chiralcel OD-RH C18 column. Their absolute configurations were elucidated by calculated ECD. Biological investigations showed that compounds 5 and 7 exhibited potent anti-inflammatory activities on LPS-stimulated NO production in BV-2 microglial cells, with IC50 values of 2.46 and 3.14µM, respectively.