Preparation,COX-2 Inhibition and Anticancer Activity of Sclerotiorin Derivatives

The latest research has indicated that anti-tumor agents with COX-2 inhibitory activity may benefit their anti-tumor efficiency. A series of sclerotiorin derivatives have been synthesized and screened for their cytotoxic activity against human lung cancer cells A549, breast cancer cells MDA-MB-435 using the MTT method. Among them, compounds 3, 7, 12, 13, 15, 17 showed good cytotoxic activity with IC₅₀ values of 6.39, 9.20, 9.76, 7.75, 9.08, and 8.18 μM, respectively. In addition, all compounds were tested in vitro the COX-2 inhibitory activity. The results disclosed compounds 7, 13, 25 and sclerotiorin showed moderate to good COX-2 inhibition with the inhibitory ratios of 58.7%, 51.1%, 66.1% and 56.1%, respectively. Notably, compound 3 displayed a comparable inhibition ratio (70.6%) to the positive control indomethacin (78.9%). Furthermore, molecular docking was used to rationalize the potential of the sclerotiorin derivatives as COX2 inhibitory agents by predicting their binding energy, binding modes and optimal orientation at the active site of the COX-2. Additionally, the structure-activity relationships (SARS) have been addressed.     

The Effect of Substituent,Degree of Acetylation and Positioning of the Cationic Charge on the Antibacterial Activity of Quaternary Chitosan Derivatives

A series of water-soluble cationic chitosan derivatives were prepared by chemoselective functionalization at the amino group of five different parent chitosans having varying degrees of acetylation and molecular weight. The quaternary moieties were introduced at different alkyl spacer lengths from the polymer backbone (C-0, C-2 and C-6) with the aid of 3,6-di-O-tert-butyldimethylsilyl protection of the chitosan backbone, thus allowing full (100%) substitution of the free amino groups. All of the derivatives were characterized using ¹H-NMR, ¹H-¹H COSY and FT-IR spectroscopy, while molecular weight was determined by GPC. Antibacterial activity was investigated against Gram positive S. aureus and Gram negative E. coli. The relationship between structure and activity/toxicity was defined, considering the effect of the cationic group’s structure and its distance from the polymer backbone, as well as the degree of acetylation within a molecular weight range of 7–23 kDa for the final compounds. The N,N,N-trimethyl chitosan with 100% quaternization showed the highest antibacterial activity with moderate cytotoxicity, while increasing the spacer length reduced the activity. Trimethylammoniumyl quaternary ammonium moieties contributed more to activity than 1-pyridiniumyl moieties. In general, no trend in the antibacterial activity of the compounds with increasing molecular weight or degree of acetylation up to 34% was observed.     

The Structure-Activity Relationship between Marine Algae Polysaccharides and Anti-Complement Activity

In this study, 33 different polysaccharides were prepared to investigate the structure-activity relationships between the polysaccharides, mainly from marine algae, and anti-complement activity in the classical pathway. Factors considered included extraction methods, fractionations, molecular weight, molar ratio of galactose to fucose, sulfate, uronic acid (UA) content, linkage, branching, and the type of monosaccharide. It was shown that the larger the molecular weights, the better the activities. The molar ratio of galactose (Gal) to fucose (Fuc) was a positive factor at a concentration lower than 10 µg/mL, while it had no effect at a concentration more than 10 µg/mL. In addition, sulfate was necessary; however, the sulfate content, the sulfate pattern, linkage and branching had no effect at a concentration of more than 10 µg/mL. Moreover, the type of monosaccharide had no effect. Laminaran and UA fractions had no activity; however, they could reduce the activity by decreasing the effective concentration of the active composition when they were mixed with the active compositions. The effect of the extraction methods could not be determined. Finally, it was observed that sulfated galactofucan showed good anti-complement activity after separation.     

Anti-Cancer and Anti-Inflammatory Activities of Three New Chromone Derivatives from the Marine-Derived Penicillium citrinum

Three new and uncommon chromone analogs, epiremisporine F (1), epiremisporine G (2), and epiremisporine H (3), were isolated from marine-origin Penicillium citrinum. Among the isolated compounds, compounds 2–3 remarkably suppressed fMLP-induced superoxide anion generation by human neutrophils, with IC₅₀ values of 31.68 ± 2.53, and 33.52 ± 0.42 μM, respectively. Compound 3 exhibited cytotoxic activities against human colon carcinoma (HT-29) and non-small lung cancer cell (A549) with IC₅₀ values of 21.17 ± 4.89 and 31.43 ± 3.01 μM, respectively, and Western blot assay confirmed that compound 3 obviously induced apoptosis of HT-29 cells, via Bcl-2, Bax, and caspase 3 signaling cascades.     

Rare Chromone Derivatives from the Marine-Derived Penicillium citrinum with Anti-Cancer and Anti-Inflammatory Activities

Three new and rare chromone derivatives, epiremisporine C (1), epiremisporine D (2), and epiremisporine E (3), were isolated from marine-derived Penicillium citrinum, together with four known compounds, epiremisporine B (4), penicitrinone A (5), 8-hydroxy-1-methoxycarbonyl-6-methylxanthone (6), and isoconiochaetone C (7). Among the isolated compounds, compounds 2–5 significantly decreased fMLP-induced superoxide anion generation by human neutrophils, with IC₅₀ values of 6.39 ± 0.40, 8.28 ± 0.29, 3.62 ± 0.61, and 2.67 ± 0.10 μM, respectively. Compounds 3 and 4 exhibited cytotoxic activities with IC₅₀ values of 43.82 ± 6.33 and 32.29 ± 4.83 μM, respectively, against non-small lung cancer cell (A549), and Western blot assay confirmed that compounds 3 and 4 markedly induced apoptosis of A549 cells, through Bcl-2, Bax, and caspase 3 signaling cascades.     

Cytotoxic Activity of Semi-Synthetic Derivatives of Elatol and Isoobtusol

In the present study, the in vitro cytotoxic effects of six semi-synthetic derivatives of elatol (1) and isoobtusol (2) were investigated. Chemical modifications were performed on the hydroxyl groups aiming to get derivatives of different polarity, namely the hemisuccinate, carbamate and sulfamate. The structural elucidation of the new derivatives was based on detailed NMR and MS spectroscopic analyses. The in vitro cytotoxicity of compounds 1 to 8 was evaluated against A459 and RD tumor cell lines with CC₅₀ values ranging from 4.93 to 41.53 µM. These results suggest that the structural modifications performed on both compounds could be considered a good strategy to obtain more active derivatives.     

Synthesis and Antitumor Activities of Derivatives of the Marine Mangrove Fungal Metabolite Deoxybostrycin

Deoxybostrycin (1) is an anthraquinone compound derived from the marine mangrove fungus Nigrospora sp. No. 1403 and has potential to be a lead for new drugs because of its various biological properties. A series of new derivatives (2–22) of deoxybostrycin were synthesized. The in vitro cytotoxicity of all the new compounds was tested against MDA-MB-435, HepG2 and HCT-116 cancer cell lines. Most of the compounds exhibit strong cytotoxicity with IC₅₀ values ranging from 0.62 to 10 μM. Compounds 19, 21 display comparable cytotoxicity against MDA-MB-435 to epirubicin, the positive control. The primary screening results indicate that the deoxybostrycin derivatives might be a valuable source of new potent anticancer drug candidates.     

水稻结实期根系活性与稻米垩白形成的相关性初步研究

 以垩白不同的籼稻品种为材料，进行了田间试验和盆钵试验。结果表明,垩白不同的品种，其结实期根系活性存在显著差异。垩白米率、垩白度与结实期根系活性呈负相关。在根系活性指标中，库容根活量与垩白的关系最密切，而根系α 萘胺氧化力、颖花根活量与垩白的相关性较低。在抽穗期施用硝态氮肥，可以明显提高根系活性，减少垩白。抽穗期施用呼吸抑制剂叠氮化钠，导致多垩白品种GD9501的根系活性大幅度下降，垩白米率和垩白度大幅度提高；但少垩白品种青六矮表现相反。不同药剂处理下，垩白米率和垩白度分别与抽穗后10 d的根系活性呈显著（r=-0.8567*）和极显著(r=-0.9211**)负相关。     

Structure Revision and Protein Tyrosine Phosphatase Inhibitory Activity of Drazepinone

From the marine-derived fungus Penicillium sumatrense (Trichocomaceae), a pair of enantiomers [(+)-1 and (−)-1] were isolated with identical 1D NMR data to drazepinone, which was originally reported to have a trisubstituted naphthofuroazepinone skeleton. In this study, we confirmed the structures of the two enantiomers as drazepinone and revised their structures by detailed analysis of extensive 2D NMR data and a comparison of the calculated ¹³C chemical shifts, ECD, VCD, and ORD spectra with those of the experiment ones. (+)-1 and (−)-1 were evaluated for their PTP inhibitory activity in vitro. (−)-1 showed selective PTP inhibitory activity against PTP1B and TCPTP with IC₅₀ values of 1.56 and 12.5 μg/mL, respectively.     

Synthesis and Bioactivities of Marine Pyran-Isoindolone Derivatives as Potential Antithrombotic Agents

2,5-Bis-[8-(4,8-dimethyl-nona-3,7-dienyl)-5,7-dihydroxy-8-methyl-3-keto-1,2,7,8-teraahydro-6H-pyran[a]isoindol-2-yl]-pentanoic acid (FGFC1) is a marine pyran-isoindolone derivative isolated from a rare marine microorganism Stachybotrys longispora FG216, which showed moderate antithrombotic(fibrinolytic) activity. To further enhance its antithrombotic effect, a series of new FGFC1 derivatives (F1–F7) were synthesized via chemical modification at C-2 and C-2′ phenol groups moieties and C-1″ carboxyl group. Their fibrinolytic activities in vitro were evaluated. Among the derivatives, F1–F4 and F6 showed significant fibrinolytic activities with EC₅₀ of 59.7, 87.1, 66.6, 82.8, and 42.3 μM, respectively, via enhancement of urokinase activity. Notably, derivative F6 presented the most remarkable fibrinolytic activity (2.72-fold than that of FGFC1). Furthermore, the cytotoxicity of derivative F6 was tested as well as expression of Fas/Apo-1 and IL-1 on HeLa cells. The results showed that, compared to FGFC1, derivative F6 possessed moderate cytotoxicity and apoptotic effect on HeLa cells (statistical significance p > 0.1), making F6 a potential antithrombotic agent towards clinical application.     

BDDE-Inspired Chalcone Derivatives to Fight Bacterial and Fungal Infections

The growing number of infectious diseases around the world threatens the effective response of antibiotics, contributing to the increase in antibiotic resistance seen as a global health problem. Currently, one of the main challenges in antimicrobial drug discovery is the search for new compounds that not only exhibit antimicrobial activity, but can also potentiate the antimicrobial activity and revert antibiotics’ resistance, through the interference with several mechanisms, including the inhibition of efflux pumps (EPs) and biofilm formation. Inspired by macroalgae brominated bromophenol BDDE with antimicrobial activity, a series of 18 chalcone derivatives, including seven chalcones (9–15), six dihydrochalcones (16–18, and 22–24) and five diarylpropanes (19–21, and 25 and 26), was prepared and evaluated for its antimicrobial activity and potential to fight antibiotic resistance. Among them, chalcones 13 and 14 showed promising antifungal activity against the dermatophyte clinical strain of Trichophyton rubrum, and all compounds reversed the resistance to vancomycin in Enterococcus faecalis B3/101, with 9, 14, and 24 able to cause a four-fold decrease in the MIC of vancomycin against this strain. Compounds 17–24 displayed inhibition of EPs and the formation of biofilm by S. aureus 272123, suggesting that these compounds are inhibiting the EPs responsible for the extrusion of molecules involved in biofilm-related mechanisms. Interestingly, compounds 17–24 did not show cytotoxicity in mouse embryonic fibroblast cell lines (NIH/3T3). Overall, the results obtained suggest the potential of dihydrochalcones 16–18 and 22–24, and diarylpropanes 19–21, 25 and 26, as hits for bacterial EPs inhibition, as they are effective in the inhibition of EPs, but present other features that are important in this matter, such as the lack of antibacterial activity and cytotoxicity.     

New 3-Acyl Tetramic Acid Derivatives from the Deep-Sea-Derived Fungus Lecanicillium fusisporum

Seven rare C3-C6 reduced 3-acyl tetramic acid derivatives, lecanicilliumins A–G (1–7), along with the known analogue cladosporiumin D (8), were obtained from the extract of the deep-sea-derived fungus Lecanicillium fusisporum GXIMD00542 within the family Clavipitacae. Their structures were elucidated by extensive spectroscopic data analysis, quantum chemistry calculations and chemical reaction. Compounds 1, 2, 5–7 exhibited moderate anti-inflammatory activity against NF-κB production using lipopolysaccharide (LPS) induced RAW264.7 cells with EC₅₀ values range of 18.49–30.19 μM.     

Synthesis of Water-Soluble Sulfonated Chitin Derivatives for Potential Antioxidant and Antifungal Activity

Chitin is a natural renewable and useful biopolymer limited by its insolubility; chemical derivatization can enhance the solubility and bioactivity of chitin. The purpose of this study was to synthesize novel water-soluble chitin derivatives, sulfo-chitin (SCT) and sulfopropyl-chitin (SPCT), as antioxidant and antifungal agents. The target derivatives were characterized by means of elemental analysis, FTIR, ¹³C NMR, TGA and XRD. Furthermore, the antioxidant activity of the chitin derivatives was estimated by free radical scavenging ability (against DPPH-radical, hydroxyl-radical and superoxide-radical) and ferric reducing power. In addition, inhibitory effects against four fungi were also tested. The findings show that antioxidant abilities and antifungal properties were in order of SPCT > SCT > CT. On the basis of the results obtained, we confirmed that the introduction of sulfonated groups on the CT backbone would help improve the antioxidant and antifungal activity of CT. Moreover, its efficacy as an antioxidant and antifungal agent increased as the chain length of the substituents increased. This derivatization strategy might provide a feasible way to broaden the utilization of chitin. It is of great significance to minimize waste and realize the high-value utilization of aquatic product wastes.     

Antibacterial Alkaloids and Polyketide Derivatives from the Deep Sea-Derived Fungus Penicillium cyclopium SD-413

Nine secondary metabolites (1–9), including two new polyketide derivatives 9-dehydroxysargassopenilline A (4) and 1,2-didehydropeaurantiogriseol E (5), along with seven known related secondary metabolites (1–3 and 6–9), were isolated and identified from the deep sea-derived fungus Penicillium cyclopium SD-413. Their structures were elucidated on the basis of 1D/2D NMR spectroscopic and mass spectrometric analysis and the absolute configurations were determined by the combination of NOESY correlations and time-dependent density functional (TDDFT) ECD calculations. Compounds 1–9 inhibited some pathogenic bacteria including Escherichia coli, E. ictaluri, Edwardsiella tarda, Micrococcus luteus, Vibrio anguillarum, and V. harveyi, with MIC (minimum inhibitory concentration) values ranging from 4 to 32 μg/mL.     

Chemistry and Tumor Cell Growth Inhibitory Activity of 11,20-Epoxy-3Z,5(6)E-diene Briaranes from the South China Sea Gorgonian Dichotella gemmacea

Eighteen new 11,20-epoxy-3Z,5E-dien briaranes, gemmacolides AA–AR (1–18), were isolated together with three known analogs, dichotellides F (19) and I (20), and juncenolide C (21), from the South China Sea gorgonian Dichotella gemmacea. The structures of the compounds were elucidated by detailed spectroscopic analysis and comparison with reported data. The absolute configuration was determined based on the ECD experiment. In the in vitro bioassay, compounds 1–3, 5, 6, 8–12, and 14–19 exhibited different levels of growth inhibition activity against A549 and MG63 cell lines. Preliminary structure-activity analysis suggests that 12-O-isovalerate may increase the activity whereas 13- or 14-O-isovalerate may decrease the activity. Contribution of substitutions at C-2 and C-16 remains uncertain.     

茶产业与安溪县经济发展关联度的实证研究

通过指标设计与数据收集,利用关联度计算方法,实证分析了茶产业与安溪县经济发展的关联度,研究表明:茶产业发展与安溪县总体经济、第一产业、第二产业和第三产业的发展均存在高度关联,茶产业的快速发展是推动安溪县经济发展的重要因素.     

Study of Structure–Activity Relationships of the Marine Alkaloid Fascaplysin and Its Derivatives as Potent Anticancer Agents

Marine alkaloid fascaplysin and its derivatives are known to exhibit promising anticancer properties in vitro and in vivo. However, toxicity of these molecules to non-cancer cells was identified as a main limitation for their clinical use. Here, for the very first time, we synthesized a library of fascaplysin derivatives covering all possible substituent introduction sites, i.e., cycles A, C and E of the 12H-pyrido[1-2-a:3,4-b’]diindole system. Their selectivity towards human prostate cancer versus non-cancer cells, as well as the effects on cellular metabolism, membrane integrity, cell cycle progression, apoptosis induction and their ability to intercalate into DNA were investigated. A pronounced selectivity for cancer cells was observed for the family of di- and trisubstituted halogen derivatives (modification of cycles A and E), while a modification of cycle C resulted in a stronger activity in therapy-resistant PC-3 cells. Among others, 3,10-dibromofascaplysin exhibited the highest selectivity, presumably due to the cytostatic effects executed via the targeting of cellular metabolism. Moreover, an introduction of radical substituents at C-9, C-10 or C-10 plus C-3 resulted in a notable reduction in DNA intercalating activity and improved selectivity. Taken together, our research contributes to understanding the structure–activity relationships of fascaplysin alkaloids and defines further directions of the structural optimization.     

Design,Semisynthesis, Insecticidal and Antibacterial Activities of a Series of Marine-Derived Geodin Derivatives and Their Preliminary Structure–Activity Relationships

To enhance the biological activity of the natural product geodin (1), isolated from the marine-derived fungus Aspergillus sp., a series of new ether derivatives (2–37) was designed and semisynthesized using a high-yielding one-step reaction. In addition, the insecticidal and antibacterial activities of all geodin congeners were evaluated systematically. Most of these derivatives showed better insecticidal activities against Helicoverpa armigera Hübner than 1. In particular, 15 showed potent insecticidal activity with an IC₅₀ value of 89 μM, comparable to the positive control azadirachtin (IC₅₀ = 70 μM). Additionally, 5, 12, 13, 16, 30 and 33 showed strong antibacterial activity against Staphylococcus aureus and Aeromonas salmonicida with MIC values in the range of 1.15–4.93 μM. The preliminary structure–activity relationships indicated that the introduction of halogenated benzyl especially fluorobenzyl, into 1 and substitution of 4-OH could be key factors in increasing the insecticidal and antibacterial activities of geodin.     

Apoptotic Activity of New Oxisterigmatocystin Derivatives from the Marine-Derived Fungus Aspergillus nomius NC06

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.     

稻根瘤状结构的发生发育及结构

稻根瘤状结构的发生发育及结构王洪隆，康玉庆，张存金（天津教育学院３０００２０；１）现在地址：法国国家农业研究院蒙彼利埃研究中心，法国蒙彼利埃）Ｉｎｉｔｉａｔｉｏｎ，ＤｅｖｅｌｏｐｍｅｎｔａｎｄＳｔｒｕｃｔｕｒｅｏｆＲｉｃｅＮｏｄｕｌａｒＳｔｒｕｃｔｕ...