Atypical Angucyclinones with Ring Expansion and Cleavage from a Marine Streptomyces sp.

A unique ring C-expanded angucyclinone, oxemycin A (1), and seven new ring-cleavage derivatives (2-5 and 9-11) were isolated from the marine actinomycete Streptomyces pratensis KCB-132, together with eight known analogues (6-8 and 12-16). Their structures were elucidated by spectroscopic analyses, single-crystal X-ray diffractions, and NMR and ECD calculations. Among these atypical angucyclinones, compound 1 represented the first seven-membered ketoester in the angucyclinone family, which sheds light on the origin of fragmented angucyclinones with C-ring cleavage at C-12/C-12a in the Baeyer-Villiger hypothesis, such as 2-4, while the related "nonoxidized" analogues 5-8 seem to originate from a diverse pathway within the Grob fragmentation hypothesis. Additionally, we have succeeded in the challenging separation of elmenols E and F (12) into their four stereoisomers, which remained stable in aprotic solvents but rapidly racemized under protic conditions. Furthermore, the absolute configurations of LS1924 and its isomers (14 and 15) were assigned by ECD calculations for the first time. Surprisingly, these two bicyclic acetals are susceptible to hydrolysis in solution, resulting in fragmented derivatives 17 and 18 with C-ring cleavage between C-6a and C-7. Compared with ring C-modified angucyclinones, ring A-cleaved 11 was more active to multiple resistant "ESKAPE" pathogens with MIC values ranging from 4.7 to 37.5 µg/mL.

Angucycline and angucyclinone derivatives from the marine-derived Streptomyces sp.

Atramycin C (1), one new angucycline bearing an O-6 rhamnose side chain, along with one new highly hydroxylated angucyclinone emycin G (2), and ten known analogs (3-12) were isolated from the marine-derived Streptomyces sp. strain BHB-032. Their structures were assigned by spectroscopic analysis and comparison with literature data. The absolute configuration of the sugar unit of 1 was assigned as 6-O-α-l-rhamnoside, based on the analysis of the coupling constants and chemical derivatization, whereas the absolute configuration of 2 was determined by X-ray diffraction. Furthermore, the stereochemistry of saccharothrixin A (3) and SNA-8073-A (4) was established unequivocally by X-ray crystallography for the first time. Compounds 1 and 2 exhibited moderate antimicrobial activities with minimum inhibitory concentration (MIC) values ranging from 16 to 64 µg/ml.

Strepyrazinone, a tricyclic diketopiperazine derivative with cytotoxicity from a marine-derived actinobacterium.

Strepyrazinone (1), a tricyclic diketopiperazine derivative with a carbon skeleton unprecedented in natural products, was isolated from the marine-derived Streptomyces sp. B223. Its structure was elucidated by spectroscopic analyses and electronic circular dichroism calculation. Compound 1 showed cytotoxic activity against HCT-116 cancer cell lines with an IC50 value of 0.34 µM.

Anti-inflammatory and anti-viral labdane diterpenoids from the fruits of Forsythia suspensa.

Eight labdane diterpenoids, including two new labdane diterpenoids, named forsyshiyanins A-B (2-3), along with six known ones (1, 4-8), were isolated from the fruits of Forsythia suspensa. The new structures including their absolute configurations were elucidated by extensive spectroscopic analyses, X-ray diffraction and computational calculation. In vitro, eight labdane diterpenoids showed anti-inflammatory activities, with the inhibition rates of release of ß-glucuronidase from polymorphonuclear leukocytes of rats being in the range 46.8-51.0% at concentrations of 10 µM, as well as anti-viral activities against influenza A (H1N1) virus and respiratory syncytial virus (RSV), with the IC50 values in the range 18.4-26.2 µM and EC50 values in the range 10.5-14.4 µM, respectively.

Isolation, stereochemical study, and racemization of (±)-pratenone A, the first naturally occurring 3-(1-naphthyl)-2-benzofuran-1(3H)-one polyketide from a marine-derived actinobacterium.

(±)-Pratenone A (1), the first representative of natural 3-(1-naphthyl)-2-benzofuran-1(3H)-one polyketides, was isolated from a marine-derived Streptomyces pratensis strain KCB-132 together with three other new analogues (2-4). Its structure was assigned by spectroscopic analysis, and the absolute configurations of the two enantiomers separated by high-performance liquid chromatography were determined by single-crystal X-ray diffraction and electronic circular dichroism calculations. The solvent-induced racemization of 1 and a proposed biogenetic pathway to 1-4 from the co-isolated angucyclinone precursor, as well as their biological activity, are also discussed.

Complete Genome Sequence of Streptomyces olivoreticuli ATCC 31159 Which can Produce Anticancer Bestatin and Show Diverse Secondary Metabolic Potentials.

Because of its competitive inhibitor activity against aminopeptidase B, bestatin isolated from the broth of Streptomyces olivoreticuli ATCC 31159 is famous and currently used as an approved therapeutic agent for cancer and bacterial infections. It can be used alone or in combination with other antibiotics or anticancer drugs as adjuvant therapy drug for chemotherapy and radiotherapy. Due to the therapeutic importance of bestatin, mining of its biosynthetic mechanism is imperative. Genome mining, one of the bioinformatics-based approaches for the discovery of novel natural product, has been developed and applied widely. Herein, we reported the complete genome of Streptomyces olivoreticuli ATCC 31159 obtained from American Type Culture Collection (ATCC). It consists of 8,809,793 base pairs with a linear chromosome, GC content of 71.1%, 7520 protein-coding genes, 75 tRNA operons, 21 rRNA operons, 63 sRNAs. In addition, predictive analysis showed that at least 37 putative biosynthetic gene clusters (BGCs) of the secondary metabolites were obtained, 18 new BGCs with low similarity (< 25%) were included. The availability of novel and abundant gene clusters not only will provide clues for cracking the biosynthetic mechanism of bestatin, but also will provide valuable insight for mining the diverse bioactive compounds based on rational strategies.

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.

Minor protopanaxadiol type sapogenins from the alkali hydrolysate of stems-leaves of Panax notoginseng.

Two new protopanaxadiol type sapogenins, (3ß,12ß)-3,12,20-trihydroxydammar-24-en-26-al (1) and (3ß,12ß)-3,12,20-trihydroxydammar-24-en-26-oic acid (2), were isolated from the alkali hydrolysate of stems-leaves of Panax notoginseng, along with seven known analogues (3-9). Their structures were elucidated by spectroscopic analyses and single-crystal X-ray diffraction. Compound 2 and the known sapogenins 5-8 displayed weak to moderate inhibition of NO production in LPS-induced RAW264.7 macrophages with IC50 values from 44.5 to 143.6 µM, respectively.

Trinorlabdane diterpenoid alkaloids featuring an unprecedented skeleton with anti-inflammatory and anti-viral activities from Forsythia suspensa.

Two unique trinorlabdane diterpenoid alkaloids, forsyqinlingines A (1) and B (2), were isolated from the ripe fruits of Forsythia suspensa. Their structures, including absolute stereochemical configurations, were fully elucidated from extensive spectroscopy experiments, single-crystal X-ray diffraction, and electronic circular dichroism (ECD). In addition, a plausible biosynthetic pathway for the formation of compounds 1 and 2 in Forsythia suspensa was also proposed. In vitro, the two C17-labdane diterpenoid alkaloids exhibited anti-inflammatory activities by inhibiting the release of ß-glucuronidase in rat polymorphonuclear leukocytes (PMNs), and antiviral activities against influenza A (H1N1) virus and respiratory syncytial virus (RSV).

Alkaloids bearing rare skeletons from Forsythia suspensa with anti-inflammatory and anti-viral activities in vitro.

Five alkaloids, including two previously undescribed alkaloids, named forsyshiyanines A and B, attributable to the rare skeletons 4b,5,6,7,8,8a,9,10-octahydrobenzo[f]quinoline and (6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl)methyl, respectively, along with three known ones (3-5), were isolated from the ripe fruits of Forsythia suspensa. The chemical structures including absolute configurations of two undescribed compounds were established using integrated spectroscopic techniques, electronic circular dichroism calculations, and single-crystal x-ray diffraction analysis. In vitro, five alkaloids showed anti-inflammatory activities, with the inhibition rates of the release of ß-glucuronidase from polymorphonuclear leukocytes of rats being in the range 47.9%-56.0% at a concentration of 10 µM. Moreover, five compounds exhibited anti-viral activities against influenza A virus and respiratory syncytial virus, with IC50 values in the range of 7.3-32.5 µM and EC50 values in the range 3.7-14.1 µM.

Labdane diterpenoids from Forsythia suspensa with anti-inflammatory and anti-viral activities.

Five previously undescribed labdane diterpenoids, named Forsypensins A-E, were isolated from the fruits of Forsythia suspensa. The structures and relative configurations of the compounds were elucidated via extensive spectroscopic methods, and their absolute configurations were fully confirmed by single crystal X-ray diffraction analyses using Cu Kα radiation and electronic circular dichroism data. The five labdane diterpenoids showed in vitro anti-inflammatory activity in rat polymorphonuclear leukocytes, inhibiting the rates of ß-glucuronidase release by 43.6%-49.2% at concentrations of 10 µM. The compounds also had anti-viral activity against influenza A (H1N1) virus and respiratory syncytial virus (RSV), with IC50 values in the range 21.8-27.4 µM, and EC50 values in the range 10.5-15.4 µM, respectively.

Antimicrobial and cytotoxic juglones from the immature exocarps of Juglans mandshurica.

Juglonols A-C (1-3), three new juglone derivatives possessing a hydroxyethyl side chain, were isolated from an organic extract of the immature exocarps of Juglans mandshurica together with five known tetralones (4-8). Their structures were elucidated by extensive spectroscopic analyses and comparison with literature data. The new juglone derivatives exhibited inhibitory activities towards a panel of bacteria and fungi, as well as cancer cell lines. In contrast, the known tetralone homologues (4-8) appeared to be much less efficacy.

Anti-inflammatory and immune response regulation of Si-Ni-San in 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Ni-San (SNS) is a well-known decoction in traditional Chinese medicine. Although studies have indicated that the anti-inflammatory and anti-allergic properties of SNS and its components can account for their therapeutic effects, the role and mechanism of SNS in treating skin dysfunction remain unclear. AIM OF THE STUDY: Atopic dermatitis (AD), a disorder known for its prevalence in infants and adults, severely influences the quality of life of affected patients. In this study, we aimed to investigate the anti-inflammatory and immune response modulations of SNS in 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin dysfunction. MATERIALS AND METHODS: Dermatitis was induced in Kunming mice by the topical application of DNCB. SNS or dexamethasone (positive control) was topically applied every day over the course of the 21-day study. The following were assessed: dermatitis severity scores; ear and dorsal skin haematoxylin and eosin staining; interleukin (IL)- 1α, IL-1ß, IL-2, IL-4, IL-6, and tumour necrosis factor (TNF)-α cytokine levels in the serum; spleen index; spleen CD4 + /CD8 + T lymphocyte ratio; and phosphorylation levels of mitogen-activated protein kinases (MAPKs- p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK)), IκB-α, and nuclear factor (NF)-κB (p65) in skin lesions. RESULTS: SNS significantly alleviated the symptoms of AD-like lesions induced by DNCB, decreased the infiltration of inflammatory cells in the ear and dorsal tissues, suppressed the increased cytokine levels in the serum, reduced the CD4 + /CD8 +T lymphocyte ratio in the spleen, and downregulated the activation of MAPKs, IκB-α, and NF-κB (p65) in the dorsal skin. The effects were similar to those of dexamethasone. CONCLUSIONS: SNS alleviated the DNCB-induced AD-like skin dysfunction in mice through anti-inflammatory and immune system modulation, indicating that SNS shows potential for AD treatment in clinical settings.

Leucine-derived cyanoglucosides from the aerial parts of Sorbaria sorbifolia (L.) A. Braun.

Six new cyanoglucosides, 2S-cardiospermin-5-benzoate (1), 2R-cardiospermin-5-p-hydroxybenzoate (2), 2S-cardiospermin-5-cis-p-coumarate (3), isocardiospermin-5-p-hydroxybenzoate (4), sutherlandin-5-p-hydroxybenzoate (5), and sutherlandin-5-cis-p-coumarate (6), together with 17 known compounds were isolated from Sorbaria sorbifolia. The structures of the new compounds were elucidated by extensive spectroscopic methods, including 1D and 2D NMR, HR-ESI-MS and ECD experiments. The biosynthetic relationship of 1-9 was also discussed. The cyanoglucosides (1-9) and 15 exhibited moderate inhibitory effect on nitric oxide production of RAW264.7 macrophages stimulated by lipopolysaccharide (LPS).