Synthesis and Antibacterial Activity Evaluation of Biphenyl and Dibenzofuran Derivatives as Potential Antimicrobial Agents against Antibiotic-Resistant Bacteria.

The escalating prevalence of antibiotic-resistant bacteria has led to a serious global public health problem; therefore, there is an urgent need for the development of structurally innovative antibacterial agents. In our study, a series of biphenyl and dibenzofuran derivatives were designed and synthesized by Suzuki-coupling and demethylation reactions in moderate to excellent yields (51-94% yield). Eleven compounds exhibited potent antibacterial activities against the prevalent antibiotic-resistant Gram-positive and Gram-negative pathogens, among which compounds 4'-(trifluoromethyl)-[1,1'-biphenyl]-3,4,5-triol (6i) and 5-(9H-carbazol-2-yl) benzene-1,2,3-triol (6m) showed the most potent inhibitory activities against methicillin-resistant Staphylococcus aureus and multidrug-resistant Enterococcus faecalis with MIC (minimum inhibitory concentration) values as low as 3.13 and 6.25 µg/mL, respectively. Compounds 3',5'-dimethyl-[1,1'-biphenyl]-3,4,4',5-tetraol (6e), 4'-fluoro-[1,1'-biphenyl]-3,4,5-triol (6g), and 4'-(trifluoromethyl)-[1,1'-biphenyl]-3,4,5-triol (6i) showed comparable inhibitory activities with ciprofloxacin to Gram-negative bacterium carbapenems-resistant Acinetobacter baumannii. Study of the structure-activity relationship indicated that a strong electron-withdrawing group on the A ring and hydroxyl groups on the B ring of biphenyls were beneficial to their antibacterial activities, and for benzo-heterocycles, N-heterocycle exhibited optimal antibacterial activity. These results can provide novel structures of antibacterial drugs chemically different from currently known antibiotics and broaden prospects for the development of effective antibiotics against antibiotic-resistant bacteria.

A 3D screening approach identifies the compound epitajixanthone hydrate as a new inhibitor of cancer cell growth and invasion.

With unique advantages, the small-molecule anticancer drugs have recently gained growing attention. Particular strategies, exemplified by high-throughput screening, fragment-based drug discovery, virtual screening and knowledge-based design, have been developed to identify active compounds. However, such screens generally rely on sophisticated and expensive instrumentations. Herein, we developed a simple spheroids 3D culture system to enable direct screening of small molecules with reliable results. Using this system, we screened 27 fungal natural products and three fungal crude extracts for their inhibitory effects on cancer cell growth, and invasion. We identified that the compound M23 (epitajixanthone hydrate, a derivative of prenylxanthone) and the crude extracts (MPT-191) from the fungi Taxus chinensis showed potential anticancer activity. The effect of epitajixanthone hydrate on cancer cell growth and invasion were further confirmed by the assays of cells viability, trans-well migration and invasion, colony formation and cells reattachment. Overall, Epitajixanthone hydrate was identified as an effective inhibitor of cancer cell growth and invasion by our simple and fast screening platform.

Cytotoxic Activity of Inositol Angelates and Tirucallane-Type Alkaloids from Amoora Dasyclada.

Three new inositol angelate compounds (1-3) and two new tirucallane-type alkaloids (4 and 5) were isolated from the Amoora dasyclada, and their structures were established mainly by means of combination of 1D and 2D nuclear magnetic resonance and HR-ESI-MS. Based on cytotoxicity testing, compounds 4 and 5 exhibited significant cytotoxic activity against human cancer cell line HepG2 with IC50 value at 8.4 and 13.2 µM. In addition, compounds 4 and 5 also showed remarkable growth inhibitory activity to Artemia salina larvae.

Aureonitols A and B, Two New C13 -Polyketides from Chaetomium globosum, an Endophytic Fungus in Salvia miltiorrhiza.

Two new C13 -polyketides, aureonitols A and B (1 and 2), along with five known compounds (3-7), were isolated from the solid fermentation culture of the plant endophytic fungus Chaetomium globosum from the aerial parts of Salvia miltiorrhiza. The structures and absolute configurations of 1 and 2 were determined by comprehensive spectroscopic data analysis and computed methods. Compound 5 was found to display the remarkable antimicrobial activities against four multidrug-resistant bacteria (Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, and Staphylococcus epidermidis) with MIC values of 3.13-6.25 µg/mL (ciprofloxacin: 0.78-1.56 µg/mL), and also against all tested fungal strains with MIC values of 3.13-25 µg/mL (ketoconazole: 0.78-12.50 µg/mL).

Field comparison of the effectiveness of agricultural and nonagricultural organic wastes for aided phytostabilization of a Pb-Zn mine tailings pond in Hunan Province, China.

To date, very few attempts have been made to systematically compare the effectiveness of agricultural and nonagricultural organic wastes for aided phytostabilization of mine tailings under field conditions. In this study, we performed a field trial to compare the effectiveness of three agricultural organic wastes: chicken manure (CM), crop straw (CS), and spent mushroom compost (SMC), with that of three nonagricultural organic wastes, municipal sludge (MS), medicinal herb residues (MHR), and sweet sorghum vinasse (SSV) for aided phytostabilization of a Pb-Zn mine tailings pond in Hunan Province, China. Eight plant species naturally established in the vicinity of the mine were selected and seeded onto trial plots. It was found that the CM-amended plots had the highest (p < 0.05) vegetation cover (86%) and biomass production (881 g m-2), compared to other treatments. CM was also one of the best amendments in terms of improving soil nutrient status, increasing activities of soil enzymes, and immobilizing soil Pb. In addition, CM-amended plots were characterized by their higher microbial diversity and distinct microbial community structure as compared to the control plots. MS was the second best amendment in promoting vegetation cover (71%) and biomass production (461 g m-2), and it performed as well as CM for improving nutrient status, immobilizing heavy metals, and increasing the activities of enzymes in the mine tailings. Suggestions for further lines of research are made in order to develop future investigations.

Isolation, stereochemical study, and cytotoxic activity of isobenzofuran derivatives from a marine Streptomyces sp.

A new 1,3-dihydroisobenzofuran derivative (), together with its epimer (), was isolated from marine Streptomyces sp. W007. The structure of the two compounds was established by extensive spectroscopic analysis and comparison with reported data. The absolute configurations of and were determined by a combination of experimental and computational means, including J-coupling analysis and nuclear Overhauser effect spectroscopy (NOESY) spectra, nuclear magnetic resonance (NMR) calculations, electronic circular dichroism (ECD), and optical rotation (OR) calculations. Compound had no cytotoxicity against human lung adenocarcinoma cell line A549, while compound exhibited weak activity, suggesting that the biological activity depends on the configuration of a single chirality center.

[Chemical constituents of Hyptis rhomboidea and their antifungal activity].

The present work is to investigate the chemical constitutions of Hyptis rhomboidea and their antifungal activities. The compounds were isolated by Toyopearl HW-40, Sephadex LH-20, MCI-Gel CHP-20, RP-18, PTLC and silica column chromatographic methods and subjected to evaluate some monomers antifungal activity of eight kinds of plant pathogenic bacteria. Eleven compounds were isolated and identified as ethyl caffeate (1), ursolic acid (2), oleanolic acid (3), vanillactic acid (4), methyl rosmarinate (5), kaempferol 3-O-alpha-L-rhamnopyranosyl-(1 --> 6) -beta-D-glucopyranoside (6), kaempferol 3-O-alpha-L-rhamnopyranosyl-(1 --> 6)-beta-D-glucopyranoside (7), ilexgenin A (8), beta-amyrin (9), kaempferol 3-O-beta-D-glucopyranoside (astrgalin, 10) and cholest-5-ene-3beta, 4beta-diol (11). Compound 1 showed the strongest inhibitory effect on Sclerotinia sclerotiorum with the MIC 16.2 mg x L(-1), and compound 5 showed the strongest inhibitory effect on S. minor and Exserohilum turcicum with MIC 16.2, 8.1 mg x L(-1), respectively. All compounds were isolated from the H. rhomboidea for the first time, and compounds 1 and 5 showed antifungal activity.

Cytotoxic azaphilone alkaloids from Chaetomium globosum TY1.

Three novel azaphilone alkaloids, namely chaetomugilides A-C (1-3), together with three related compounds (4-6) were isolated from the methanol extract of Chaetomium globosum TY1, an endophytic fungus isolated from Ginkgo biloba. Their structures were elucidated on the basis of extensive 1D and 2D NMR as well as HRESI-MS spectroscopic data analysis. The isolated compounds exhibited highly cytotoxic activities against human cancer cell line HePG2 with the IC50 values range from 1.7 to 53.4µM.

Bioactive secondary metabolites from endophytic strains of Neocamarosporium betae collected from desert plants.

Endophytic fungi from desert plants belong to a unique microbial community that has been scarcely investigated chemically and could be a new resource for bioactive natural products. In this study, 13 secondary metabolites (1-13) with diverse carbon skeletons, including a novel polyketide (1) with a unique 5,6-dihydro-4H,7H-2,6-methanopyrano[4,3-d][1,3]dioxocin-7-one ring system and three undescribed polyketides (2, 7, and 11), were obtained from the endophytic fungus Neocamarosporium betae isolated from two desert plant species. Different approaches, including HR-ESI-MS, UV spectroscopy, IR spectroscopy, NMR, and CD, were used to determine the planar and absolute configurations of the compounds. The possible biosynthetic pathways were proposed based on the structural characteristics of compounds 1-13. Compounds 1, 3, 4, and 9 exhibited strong cytotoxicity toward HepG2 cells compared with the positive control. Several metabolites (2, 4-5, 7-9, and 11-13) were phytotoxic to foxtail leaves. The results support the hypothesis that endophytic fungi from special environments, such as desert areas, produce novel bioactive secondary metabolites.

Fusaroside, a unique glycolipid from Fusarium sp., an endophytic fungus isolated from Melia azedarach.

Fusaroside (1), a unique trehalose-containing glycolipid composed of the 4-hydroxyl group of a trehalose unit attached to the carboxylic carbon of a long-chain fatty acid, was isolated from the organic extract of fermentation broths of an endophytic fungus, Fusarium sp. LN-11 isolated from the leaves of Melia azedarach. Six known compounds, phalluside (2), (9R*,10R*,7E)-6, 9,10-trihydroxyoctadec-7-enoic acid (3), porrigenic acid (4), (9Z)-2,3-dihydroxypropyl octadeca-9-enoate (5), cerevisterol (6) and ergokonin B (7), were also isolated from this fungus. The glycolipid contains a rare branched long-chain fatty acid (C(20:4)) with a conjugated diene moiety and a conjugated ketone moiety. The structure of the new compound 1 was elucidated by spectroscopic methods (1D and 2D NMR experiments, MS) and chemical degradations. The metabolites 1-5 were shown to have moderate to weak active against the brine shrimp larvae. To our knowledge, this is the first report of isolation of the first representative of a new family of glycolipids from natural sources.

Absolute configuration of fusarone, a new azaphilone from the endophytic fungus Fusarium sp. isolated from Melia azedarach, and of related azaphilones.

A new azaphilone derivative, named fusarone (1), has been isolated from the ethyl acetate soluble extract of the fermentation broth of an endophytic fungus, Fusarium sp. LN-12, isolated from the leaves of Melia azedarach Linn. The structure of the new compound was established on the basis of extensive spectroscopic analysis, including 1D-NMR and 2D-NMR ((1) H-(1)H COSY, TOCSY, HSQC, HMBC, and NOESY) experiments. The absolute configurations of fusarone (1) and of a second related azaphilone were determined by means of electronic circular dichroism spectroscopy and optical rotation calculations.

Undescribed specialised metabolites from the endophytic fungus Emericella sp. XL029 and their antimicrobial activities.

The fungus Emericella sp. XL029 isolated from leaves of Panax notoginseng was investigated for agents with potential antibacterial and antifungal activities using a one strain-many compounds (OSMAC) strategy. Fifteen compounds, including seven undescribed structures, were obtained from this species. Their structures were confirmed by extensive spectroscopic data, single-crystal X-ray crystallography and quantum chemistry calculations. Emerlactam A exhibited better antibacterial activity against multidrug-resistant Enterococcus faecium and antifungal activity against Helminthosporium maydis, with an MIC value of 12.5 µg/mL. Quiannulatic acid displayed significant antibacterial activity against multidrug-resistant Enterococcus faecium and multidrug-resistant Enterococcus faecalis with MIC values of 1.56 µg/mL and 3.13 µg/mL, respectively. 5-alkenylresorcinol exhibited significant antifungal activity against all tested phytopathogenic fungi with MIC values ranging from 6.25 to 12.5 µg/mL.

RETRACTED: Sannastatin, a novel toxic macrolactam polyketide glycoside produced by actinomycete Streptomyces sannanensis.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. One of the co-authors, Hartmut Laatsch, informed the journal that this paper was submitted and published without his consent. This is a violation of the journal's policy that all authors of a paper should approve submission of a manuscript. Apologies are offered to readers of the journal that this was not detected during the submission and evaluation process.

Toxic polyketides produced by Fusarium sp., an endophytic fungus isolated from Melia azedarach.

A new isocoumarin derivative named fusariumin (1), together with two known related resorcylic acid lactones aigialomycin D (2) and pochonin N (3), has been isolated from the cultures of Fusarium sp. LN-10, an endophytic fungus originated from the leaves of Melia azedarach. Their structures were established on the basis of extensive spectroscopic analyzes including 1D- and 2D- NMR ((1)H-(1)H COSY, HSQC, HMBC, and NOESY) experiments. Compounds 1-3 displayed significant growth inhibitory activity against the brine shrimp (Artemia salina).

[Ecological Effects of Species Diversity on Plant Growth and Physico-Chemical Properties in a Pb-Zn Mine Tailings].

The remediation of metalliferous mine tailings remains a challenge in many regions of the world. A field experiment was conducted on representative Pb-Zn mine tailings with different species richness (1-, 4-, 8-, and 16-species) to evaluate the potential roles of species diversity in the phytoremediation of metalliferous mine tailings. The main results were ① high species diversity greatly enhanced vegetation cover and biomass. For example, the average vegetation cover and biomass were 33.4% and 66.7 g ·m-2 in 1-species plots and reached 78.4% and 183.8 g ·m-2 in 16-species plots, respectively. ② Plant species diversity had significant effects on nutrient accumulation. Total organic carbon (TOC), water organic carbon (SOC), total nitrogen (TN) and total phosphorus (TP) significantly increased with the species diversity (TOC:r=0.30,P<0.001; SOC:r=0.20,P<0.05; TN:r=0.24,P<0.05; TP:r=0.20,P<0.05). ③ Species diversity not only reduced the concentration of diethylenetriamine pentaacetate (DTPA)-extracted metals in the mine tailings, but also decreased heavy metal transfer and accumulation in the soil-plant system. With enhanced species diversity, DTPA-extracted Cd, Cu, Pb, and Zn decreased significantly (DTPA-Cd:r=0.20,P<0.05; DTPA-Cu:r=0.19, P<0.05; DTPA-Pb:r=0.23, P<0.05; DTPA-Zn:r=0.23, P<0.05). With increasing species diversity, a slightly decreasing trend was observed for Cd, Cu, Pb, and Zn concentrations in the aboveground parts of plants (Cd:r=-0.16, P<0.01; Cu:r=-0.23, P<0.001; Pb:r=-0.15, P<0.05; Zn:r=-0.18, P<0.001). In conclusion, plant diversity can play an important role in mine reclamation.

Eremophilane Sesquiterpenoids with Antibacterial and Anti-inflammatory Activities from the Endophytic Fungus Septoria rudbeckiae.

Fourteen eremophilane sesquiterpenoids (1-14), including nine new congeners, septoreremophilanes A-I (1-9), together with three known sesquiterpenes (15-17), two known tetralone derivatives (18, 19), and two known cholesterol analogues (20, 21), were isolated from the endophytic fungus Septoria rudbeckiae. Compounds 1-6 and 7a belong to the family of the highly oxygenated eremophilane sesquiterpenoids with a 6/6/5 tricyclic system and bearing a hemiacetal moiety. The inhibitions of all metabolites against eight bacteria were estimated in vitro, and nine new metabolites (1-9) were tested for antineuroinflammatory activity. Notably, the effects of 4 against Pseudomonas syringae pv. actinidae and 20 against Bacillus cereus displayed potent inhibitory, with the MIC values of 6.25 and 6.25 µM, respectively. Further, scanning electron microscopy analyses indicated that 4 and 20 were to change the outer configuration of bacterial cells, respectively, and the investigations demonstrated that 4 and 20 may act as potential structure templates for the development of the agrochemical bactericides. Additionally, compound 6 displayed potent inhibition of NO generation in lipopolysaccharide-induced BV-2 microglial cells (IC50 = 12.0 ± 0.32 µM), and the conceivable anti-inflammatory mechanisms implicated were also investigated by molecular docking. Thus, the bioactive metabolites of the strain S. rudbeckiae may serve as a novel resource to be developed.

Bioactive metabolites produced by Chaetomium globosum, an endophytic fungus isolated from Ginkgo biloba.

A novel cytotoxic chlorinated azaphilone derivative named chaetomugilin D (1), together with three known metabolites, chaetomugilin A (2), chaetoglobosins A (3) and C (4), has been isolated by a bioassay-guided fractionation from the EtOAc extract of the cultures of Chaetomium globosum, an endophytic fungus found in the leaves of Ginkgo biloba. Structure of 1 was established by analyses of spectroscopic methods, including 2D-NMR experiments (COSY, NOESY, HMQC, and HMBC). Compounds 1-4 displayed significant growth inhibitory activity against the brine shrimp (Artemia salina) and Mucor miehei.

catena-Poly[[aqua-trimethyl-tin(IV)]-{[trimethyl-tin(IV)]-µ(3)-thio-phene-2,5-dicarboxyl-ato}].

In the title compound, [Sn(2)(CH(3))(6)(C(6)H(2)O(4)S)(H(2)O)](n), each of the two crystallographically independent Sn atoms exhibits a distorted trigonal-bipyramidal coordination geometry formed by two O and three C atoms. The coordinated water mol-ecule plays an important role in crystal packing consolidation via O-H⋯O hydrogen bonding.