Retymicin, galtamycin B, saquayamycin Z and ribofuranosyllumichrome, novel secondary metabolites from Micromonospora sp. Tü 6368. II. Structure elucidation

A detailed screening of the secondary metabolite pattern from Micromonospora sp. strain Tü 6368 resulted in the isolation of ten compounds belonging to five different structural families. The structures of the novel compounds 1-(alpha-ribofuranosyl)-lumichrome (3), retymicin (7), galtamycin B (11) and saquayamycin Z (14) were assigned by spectroscopic methods and chemical transformations. This strain fits our hypothesis that the metabolite analysis of biosynthetically talented strains leads readily to novel compounds.     

Streptocidins A-D, novel cyclic decapeptide antibiotics produced by Streptomyces sp. Tü 6071. I. Taxonomy, fermentation, isolation and biological activities

Four novel cyclic homodecapetide antibiotics, streptocidins A-D were detected in the mycelium extract of Streptomyces sp. Tü 6071 by HPLC-diode-array and HPLC-electrospray-mass-spectrometry screening. The peptides which were closely related in structure to the tyrocidines and gramicidins of Bacillus brevis show antibiotic activities against Gram-positive bacteria.     

Simocyclinones, novel cytostatic angucyclinone antibiotics produced by Streptomyces antibioticus Tü 6040. I. Taxonomy, fermentation, isolation and biological activities

Two novel angucyclinone-type antibiotics, simocyclinones D4 and D8, were detected in the mycelium extract of Streptomyces antibioticus Tü 6040 by HPLC-diode-array and HPLC-electrospray-mass-spectrometry screening. The compounds show antibiotic activities against Gram-positive bacteria and cytostatic effects on various tumor cell lines.     

Arylomycins A and B,new biaryl-bridged lipopeptide antibiotics produced by Streptomyces sp. Tü 6075. I. Taxonomy,fermentation, isolation and biological activities

New lipopeptide antibiotics, colourless arylomycins A series and yellow arylomycins B series were detected in the culture filtrate and mycelium extracts of Streptomyces sp. Tü 6075 by HPLC-diode-array and HPLC-electrospray-mass-spectrometry screening. Arylomycins are a family of lipohexapeptide antibiotics, which represent the first examples of biaryl-bridged lipopeptides. They show antibiotic activities against Gram-positive bacteria.     

Ripromycin and other polycyclic macrolactams from Streptomyces sp. Tü 6239: taxonomy,fermentation, isolation and biological properties

Strain Tü 6239 was isolated from a soil sample collected in Brazil and determined as a new species of the genus Streptomyces. In the course of our HPLC-diode array screening program three metabolites were detected in the culture filtrate and mycelium extracts of strain Tü 6239. They were characterised as members of the macrolactam group, the new compound ripromycin (1), the previously described ikarugamycin (2) and a new derivative of it, ikarugamycin epoxide (3). They show antibiotic activities against gram-positive bacteria and cytostatic effects to various human tumor cell lines.     

Phenalinolactones A-D, terpenoglycoside antibiotics from Streptomyces sp. Tü 6071

Four new terpenoglycoside antibiotics, phenalinolactones A-D were isolated from Streptomyces sp. Tü 6071. The structures were elucidated on the basis of detailed NMR and MS analyses. Phenalinolactones combine a diterpenoid tricycle, a 2,3,6-trideoxysugar, a pyrrole-carboxylic acid and an uncommonly oxidized unsaturated γ-lactone in a unique manner. Phenalinolactones show an inhibitory activity against gram-positive bacteria.     

Arylomycins A and B,new biaryl-bridged lipopeptide antibiotics produced by Streptomyces sp. Tü 6075. II. Structure elucidation

The structures of new lipopeptide antibiotics, arylomycins A and B, were elucidated by a combination of ESI-FTICR-mass spectrometry, NMR spectroscopy, Edman sequencing, and fatty acid and chiral amino acid analyses. The colourless arylomycins A share the peptide sequence of D-N-methylseryl2(D-MeSer2)-D-alanyl3-glycyl4-N-methyl- 4-hydroxyphenylglycyl5(MeHpg5)-L-alanyl6-tyrosine7 cyclised by a [3,3]biaryl bond between MeHpg5 and Tyr7. The yellow arylomycins B differ from arylomycins A by nitro substitution of Tyr7. The N-termini of arylomycins A and B are acylated with saturated C11-C15 fatty acids (fa1) comprising n, iso, and anteiso isomers. Arylomycins A and B represent the first examples of biaryl-bridged lipopeptides.     

Investigations on the metabolic pathways of cyclosporine: I. Excretion of cyclosporine and its metabolites in human bile—isolation of 12 new cyclosporine metabolites

1. Cyclosporine metabolites of known and unknown structures were isolated, by semi-preparative?h.p.l.c., from human bile from the T-tube of liver-grafted patients, who received cyclosporine treatment. Their structures were elucidated by FAB mass spectrometry and ¹H-n.m.r. spectroscopy.

2. Twelve of the cyclosporine metabolites, with known chemical structures, were isolated and identified using authentic standard material.

3. Four isolated fractions contained tri-hydroxylated metabolites; two fractions contained di-hydroxylated, demethylated metabolites; one fraction contained a trihydroxylated, demethylated metabolite; and one fraction a mono-hydroxylated, demethylated metabolite. The exact metabolism sites were partially defined.

4. Two carboxylated cyclosporine metabolites, of which one was hydroxylated in an unknown position, were isolated.

5. One new metabolite proved to be a glucuronylated phase II metabolite. Deglucuronylation of this metabolite by β-glururonidase yielded metabolite AM1c. The proposed structure was AM1c-Gic; is a proposed extension of the Hawk's Cay nomenclature of the cyclosporine metabolites for glucuronylated metabolites.

6. One of the unknown metabolites was hydroxylated in two positions of amino acid 1. The proposed nomenclature was ‘AM11d’, where ‘1d’ indicates hydroxylation at the δC of amino acid 1.

7. A metabolite with an aldehyde functional group at amino acid 1, which had two isomeric forms, was isolated. I.r.-spectroscopy indicated that isomerism may be caused by conjugation of the aldehyde group with the double bond between C6 and C7 of amino acid 1.     

Cytotoxicity and secondary metabolites production in terrestrial Nostoc strains,originating from different climatic/geographic regions and habitats: Is their cytotoxicity environmentally dependent?

Extensive selection of cyanobacterial strains (82 isolates) belonging to the genus Nostoc, isolated from different climatic regions and habitats, were screened for both their secondary metabolite content and their cytotoxic effects to mammalian cell lines. The overall occurrence of cytotoxicity was found to be 33%, which corresponds with previously published data. However, the frequency differs significantly among strains, which originate from different climatic regions and microsites (particular localities). A large fraction of intensely cytotoxic strains were found among symbiotic strains (60%) and temperate and continental climatic isolates (45%); compared with the less significant incidences in strains originating from cold regions (36%), deserts (14%), and tropical habitats (9%). The cytotoxic strains were not randomly distributed; microsites that clearly had a higher occurrence of cytotoxicity were observed. Apparently, certain natural conditions lead to the selection of cytotoxic strains, resulting in a high cytotoxicity occurrence, and vice versa. Moreover, in strains isolated from a particular microsite, the cytotoxic effects were caused by different compounds. This result supports our hypothesis for the environmental dependence of cytotoxicity. It also contradicts the hypothesis that clonality and lateral gene transfer could be the reason for this phenomenon. Enormous variability in the secondary metabolites was detected within the studied Nostoc extracts. According to their molecular masses, only 26% of these corresponded to any known structures; thus, pointing to the high potential for the use of many terrestrial cyanobacteria in both pharmacology and biotechnology. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2011.     

SHISEN-1,a novel phenazine antibiotic from Streptoplanospora viridis Ⅱ.Physico-chemical properties and structure elucidation

在筛选ＭＲＳＡ抑制剂的过程中，从稀有放线菌Ｓｔｒｅｐｔｏｐｌａｎｏｓｐｏｒａｖｉｒｉｄｉｓ的次级代谢产物中，得到活性化合物ＳＨＩＳＥＮ－１，该化合物为黄色粉末，于２５４及３６４ｎｍ处有最大的紫外吸收峰，经理化性质和光谱分析（ＩＲ、ＵＶ、ＦＡＢ－ＭＳ、ＥＩ－ＭＳ、１Ｈ－ＮＭＲ、１３Ｃ－ＮＭＲ、ＤＥＰＴ、ＨＭＱＣ、ＨＭＢＣ、１Ｈ－１ＨＣＯＳＹ），得知它为一个新的酚嗪类抗生素，分子式为Ｃ２２Ｈ１６Ｎ２Ｏ４。     

Isolation, structural features and antitumor activities of sixpolysaccharides from Angelica sinensis （Oliv.） diels in vitro

AIM The previous work has demonstrated that the polysaccharides of Angelica sinensis (Oliv.) Diels have significantly antitumor activity and indicated that the activity is strongly dependent on their structures. However, the relationships between the structure and the activities are still ambiguous. Thus, at present, more efforts are being expended in seeking to isolate the polysaccharides from Angelica sinensis(Oliv.) Diels, measure their structural features and antitumor activities, and elucidate structure - activity relationships of polysaccharides. METHODS The roots of Angelica sinensis ( Oliv. ) Diels were extracted With water, separated by Sephacryl S-400 and DEAE-sephadex A-25 columns and further purifled on Sephadex G-100 column.     

Juniperus oxycedrus L. subsp. oxycedrus and Juniperus oxycedrus L. subsp. macrocarpa (Sibth. & Sm.) Ball. “berries” from Turkey: Comparative evaluation of phenolic profile,antioxidant, cytotoxic and antimicrobial activities

This work aimed to evaluate and compare the phenolic profile and some biological properties of the ripe “berries” methanol extracts of Juniperus oxycedrus L. subsp. oxycedrus (Joo) and Juniperus oxycedrus L. subsp. macrocarpa (Sibth. & Sm.) Ball. (Jom) from Turkey. The total phenolic content resulted about 3-fold higher in Jom (17.89 ± 0.23 mg GAE/g extract) than in Joo (5.14 ± 0.06 mg GAE/g extract). The HPLC–DAD–ESI–MS analysis revealed a similar flavonoid fingerprint in Joo and Jom, whereas a difference in their quantitative content was found (4632 μg/g extract and 12644 μg/g extract). In addition, three phenolic acids were detected in Jom only (5765 μg/g extract), and protocatechuic acid was the most abundant one. The antioxidant capacity of the extracts was evaluated by different in vitro assays: in the DPPH and in the TBA tests a stronger activity in Jom was highlighted, while Joo exhibited higher reducing power and metal chelating activity. Joo and Jom did not affect HepG2 cell viability and both extracts resulted virtually non-toxic against Artemia salina. The extracts were also studied for their antimicrobial potential, displaying efficacy against Gram-positive bacteria.     

Extracellular polysaccharide from Bacillus sp. strain LBP32 prevents LPS-induced inflammation in RAW 264.7 macrophages by inhibiting NF-κB and MAPKs activation and ROS production

Extracellular polysaccharides (EPSs) are high-molecular weight sugar-based polymers that are synthesized and secreted by many microorganisms. Recently, EPSs have attracted particular attention due to their multiple biological functions including anti-inflammation. However, studies rarely reported the molecular mechanisms underlying their functions. We previously purified an EPS from an oligotrophic bacteria (Bacillus sp. LBP32) found in Lop Nur Desert, which possesses a potent antioxidant activity, while the anti-inflammatory effects of EPS and signaling mechanisms underlying its action have not been clarified. In this study, we demonstrated that EPS significantly inhibited the LPS-induced release of pro-inflammatory mediators, such as nitric oxide (NO), IL-6 and TNF-α, without any significant cytotoxicity. EPS also downregulated the expression of nitric oxide synthase (iNOS) induced by LPS. Furthermore, activation of nuclear factor κB (NF-κB) was abrogated by EPS through inhibited the phosphorylation of IκB kinase (IKK). Activations of Mitogen-activated protein kinases (MAPKs), including p38 MAPK and c-Jun N-terminal kinase (JNK), were also found to be inhibited by EPS. In addition, the level of intracellular reactive oxygen species (ROS) was also significantly decreased with the treatment of EPS. In vivo experiments were conducted and showed that EPS could greatly improve the outcome of mice with LPS-induced endotoxic shock. Taken together, our data indicate that EPS prevents LPS-induced inflammatory response by inhibiting NF-κB and MAPKs activation and ROS production.     

Book Review of Alcohol: No Ordinary Commodity. Research and Public Policy T. Babor,R. Caetano,S. Casswell,G. Edwards,N. Giesbrecht,K. Graham,J. Grube,P. Grunewald,L. Hill,H. Holder,R. Homel,E. Osterberg,J. Rehm,R. Room and I. Rossow. Oxford: Oxford University Press, 2003, 301 pp., £29.50 (pbk). ISBN 0 19 263261 2.

The results of the first 9 months of the implementation of a three-stage treatment programme for alcohol dependence are presented. Preparation groups (PGs) can be the main treatment option during this stage of the programme for almost all clients and Relapse Prevention groups, immediately after detoxification, for up to 75% of clients. Those participating in the PGs are doing significantly better as far as detoxification completion, 1 and 3 months post detoxification abstinence is concerned.