Showing papers in "The Journal of Antibiotics in 1997"
TL;DR: A novel bioactive depsipeptide, thiocoraline, was isolated from the mycelial cake of a marine actinomycete strain L-13-ACM2-092 and showed a potent cytotoxic activity and a strong antimicrobial activity against Gram-positive microorganisms.
Abstract: A novel bioactive depsipeptide, thiocoraline, was isolated from the mycelial cake of a marine actinomycete strain L-13-ACM2-092. Based on morphological, cultural, physiological, and chemical characteristics, strain L-13-ACM2-092 was ascribed to the genus Micromonospora. Thiocoraline showed a potent cytotoxic activity against P-388, A-549 and MEL-28 cell lines, and also a strong antimicrobial activity against Gram-positive microorganisms. This compound binds to supercoiled DNA and inhibits RNA synthesis.
205 citations
TL;DR: Thiocoraline is a new antitumor antibiotic isolated from the mycelium of Micromonospora sp.
Abstract: Thiocoraline (1) is a new antitumor antibiotic isolated from the mycelium of Micromonospora sp. L-13-ACM2-092. Its structure was elucidated to be a novel cyclic thiodepsipeptide on the basis of spectroscopic methods.
129 citations
TL;DR: Fusaricidins B, C and D, new depsipeptide antibiotics, have been isolated as minor components from the culture broth of Bacillus polymyxa KT-8 which was obtained from the rhizosphere of garlic suffering from the basal rot caused by Fusarium oxysporum.
Abstract: Fusaricidins B, C and D, new depsipeptide antibiotics, have been isolated as minor components from the culture broth of Bacillus polymyxa KT-8 which was obtained from the rhizosphere of garlic suffering from the basal rot caused by Fusarium oxysporum. The structure of fusaricidin B has been elucidated mainly by various NMR experiments coupled with amino acid analysis in relation to fusaricidin A, the main component of the complex, whose structure was reported previously. The fraction consisting of fusaricidins C and D was unsuccessfully separated, giving roughly a 4:1 mixture of the two, respectively. The structures of fusaricidins C and D have been determined within the mixture by detailed analyses of the 2D NMR spectra. Fusaricidins B, C and D are active against fungi and Gram-positive bacteria almost as well as fusaricidin A.
120 citations
TL;DR: Nocardiopsis sp.
Abstract: Nocardiopsis sp. was found to produce a new active compound designated apoptolidin (Fig. 1). In this report, we describe the production, isolation, physico-chemical properties and biological activity of apoptolidin. The producing organism was cultivated in 500mlErlenmeyer flasks containing 100ml of a medium consisting of glycerol 2.0%, molasses 1.0%, casein 0.5%, Polypepton 0.1% and CaCO3 0.4% (pH 7.2) on a rotary shaker at 27°C for 5 days. The culture broth (2liters) was centrifuged and the supernatant was extracted with EtOAc. The mycelial acetone extract was concentrated to a small volumeand then extracted with EtOAc. The combined extract was subjected to silica gel column chromatography with
114 citations
TL;DR: The findings suggest that the enhanced antibacterial activities of N-substituted derivatives of LY264826 derive from the nature of the hydrophobic side chain which can have a marked effect on dimerization and membrane binding.
Abstract: Vancomycin, LY264826 and four N-substituted derivatives of LY264826 were examined for dimerization, binding to D-alanyl-D-alanine- and D-alanyl-D-lactate-containing cell wall ligands, and binding to bacterial membrane vesicles. The six glycopeptide antibiotics represent a 360-fold range in antibacterial activities against Micrococcus luteus (MIC = 0.00072 - 0.26 μM) with the N-substituted compounds having the lowest MICs. Vancomycin, LY264826 and the four N-substituted derivatives shared nearly identical binding affinities for N, N'-diacetyl-L-lysyl-D-alanyl-D-alanine (Kb=1.5×105-5.9×105M-1). Affinities for binding N, N'-diacetyl-L-lysyl-D-alanyl-D-lactate were lower but also represented a narrow range (Kb = 0.24×103-1.6×103M-1). In contrast to ligand binding, the relative capacity of the six compounds to dimerize differed by four orders of magnitude (Kdim = 4.9×101-1.2×106M-1). The N-substituted derivatives had the highest Kdim values, required the greatest molar excess of exogenous cell wall ligand to suppress inhibition, and demonstrated a propensity to bind to bacterial membrane vesicles. The derivatives with the most lipophilic side chains were the most highly bound to vesicles. The findings suggest that the enhanced antibacterial activities of N-substituted derivatives of LY264826 derive from the nature of the hydrophobic side chain which can have a marked effect on dimerization and membrane binding.
100 citations
TL;DR: A novel fungal culture was discovered to produce two structurally unique compounds, CP-225,917 and CP-263,114, as well as zaragozic acid A (squalestatin I), which exhibits the characteristics of a sterile Phoma species.
Abstract: During the course of our screening for squalene synthase inhibitors and Ras farnesylation inhibitors, a novel fungal culture was discovered to produce two structurally unique compounds, CP-225,917 and CP-263,114, as well as zaragozic acid A (squalestatin I). The two compounds are characterized by a bicyclo[4.3.1]dec-1,6-diene core plus two extended alkyl chains. CP-225,917 and CP-263,114 inhibit Ras farnesyl transferase from rat brain with IC50 values of 6 microM and 20 microM, respectively. CP-225,917 inhibits squalene synthase with an IC50 value of 43 microM and CP-263,114 with an IC50 of 160 microM. The producing organism, though not fully classified, exhibits the characteristics of a sterile Phoma species.
99 citations
TL;DR: It is shown that viridiofungins are potent in vitro inhibitors of serine palmitoyltransferase, the first committed enzyme in sphingolipid biosynthesis, and their antifungal activity is due to inhibition of sphingoipid synthesis.
Abstract: Viridiofungins are broad spectrum antifungal agents that inhibit the squalene synthase in vitro, but do not specifically inhibit fungal ergosterol synthesis in whole cells, indicating a different mode of action for antifungal activity. In this report, we show that viridiofungins are potent in vitro inhibitors of serine palmitoyltransferase, the first committed enzyme in sphingolipid biosynthesis, and their antifungal activity is due to inhibition of sphingolipid synthesis. Additional related components with the same mode of action were isolated from the producing culture, Trichoderma viride, and inhibition of the serine palmitoyltransferase and antifungal activity is presented.
89 citations
TL;DR: In the course of the screening for new anticancer compounds produced by marine bacteria, it was found that a new genus marine bacterium Pelagiobacter variabilis produced new phenazine antibiotics, pelagiomicins A, B and C, which were labile in water and alcohols.
Abstract: In the course of our screening for new anticancer compounds produced by marine bacteria, we found that a new genus marine bacterium Pelagiobacter variabilis produced new phenazine antibiotics, pelagiomicins A, B and C. Those compounds were labile in water and alcohols. The absolute structure of the main component, pelagiomicin A, and the structures of the minor ones were determined from the spectroscopic data and by synthesis. Pelagiomicin A exhibits activity against Gram-positive and -negative bacteria and antitumor activity in vitro and in vivo.
86 citations
TL;DR: Borrelidin remarkably disrupted capillary tubes in a dose-dependent manner, by inducing apoptosis of the tube-forming cells, by suppressing angiogenesis in capillary vessels in vitro.
Abstract: Borrelidin, an antibiotic from Streptomyces rochei, was found to be an angiogenesis inhibitor in a rat aorta matrix culture model which forms capillary vessels in vitro. Borrelidin strongly inhibited capillary tube formation with a 50%-inhibitory concentration value of 0.8 nM, and decreased the number of capillary tubes within 24 hours when added after maturation of tube formation. Borrelidin remarkably disrupted capillary tubes in a dose-dependent manner, by inducing apoptosis of the tube-forming cells.
82 citations
81 citations
TL;DR: Propeptin, an inhibitor of the prolyl endopeptidase of the genus Flavobacterium competitively when Z-Gly-Pro-pNA was used as a substrate, was purified by column chromatographies on silica gel and Sephadex LH20 and high performance liquid chromatography using an ODS column.
Abstract: Propeptin, an inhibitor of the prolyl endopeptidase isolated from the mycelium of Microbispora sp. SNA-115, is an atypical cyclic peptide antibiotic. It was purified by column chromatographies on silica gel and Sephadex LH-20 and high performance liquid chromatography using an ODS column. Propeptin has the molecular formula of C113H142N26O27 and consists of nineteen amino acids. Propeptin inhibited prolyl endopeptidase of the genus Flavobacterium competitively when Z-Gly-Pro-pNA was used as a substrate. The inhibitor constant (Ki) was 0.70 microM.
TL;DR: A novel antibiotic named korormicin was isolated from the marine bacterium, Pseudoalteromonas sp.
Abstract: A novel antibiotic named korormicin was isolated from the marine bacterium, Pseudoalteromonas sp. F-420. This strain was isolated from the surface of a macro alga Halimeda sp. collected from Palau (the Republic of Belau). The planar structure of korormicin was determined by the result of 2D NMR studies and mass spectral data. Korormicin had specific inhibitory activity against marine Gram-negative bacteria, but was inactive against terrestrial microorganisms.
TL;DR: The aspergillimides are equivalent to paraherquamides which have lost both the dioxygenated 7-membered ring and the phenyl ring to which this is fused; gaining in their place a C8-keto group.
Abstract: Two members of a novel class of anthelmintics, the aspergillimides, have been isolated from the Aspergillus strain IMI 337664. This novel fungus also produced two known and one structurally novel paraherquamide. This paper describes the fermentation, isolation, structure elucidation and anthelmintic activity of aspergillimide (VM55598, 1), 16-keto aspergillimide (SB202327, 2), and the paraherquamides VM54159 (3), SB203105 (4) and SB200437 (5). The aspergillimides are equivalent to paraherquamides which have lost both the dioxygenated 7-membered ring and the phenyl ring to which this is fused; gaining in their place a C8-keto group. SB203105 is the first example of a 4-substituted paraherquamide.
TL;DR: A new tetramic acid containing metabolite, A90931a has been isolated from Streptomyces sp.
Abstract: A new tetramic acid containing metabolite, A90931a has been isolated from Streptomyces sp., along with a second factor (A90931b) recently described and known as maltophilin. The structures were determined from spectroscopic data of the isolates and their acetylated products. A90931a was spectroscopically identical to the previously described antibiotic TAN-883b whose structure was not reported. A90931a and A90931b exhibit fungicidal activity against the grape pathogen Plasmopara viticola. Due to its similarity to maltophilin, A90931a has been called dihydromaltophilin.
TL;DR: Molecular modelling of the HIV-1-protease-inhibitor complexes showed hydrogen bonding between the dihydroxybenzoquinone moiety of didemethylasterriquinone D and isocochliodinol to both active-site aspartic acids and the indole parts of the inhibitors filling the P2 and P2' pockets of the protease.
Abstract: The known bisalkylated 2, 5-dihydroxybenzoquinones didemethylasterriquinone D and iso cochliodinol as well as the new metabolites Semicochliodinol A and B have been isolated as inhibitors of HIV-1 protease from the culture broth of the fungus Chrysosporium merdarium P-5656. The structures were elucidated by spectroscopic methods. The NMR spectra of two compounds were completely assigned. The metabolites inhibit HIV-1 protease with an IC50 value as low as 0.17 μM and epidermal growth factor receptor protein tyrosine kinase at 15 to 60 μM and are therefore valuable lead compounds for these targets. Molecular modelling of the HIV-1-protease-inhibitor complexes showed hydrogen bonding between the dihydroxybenzoquinone moiety of didemethylasterriquinone D and isocochliodinol to both active-site aspartic acids (Asp25/Asp25') of the protease and the indole parts of the inhibitors filling the P2 and P2' pockets of the protease.
TL;DR: Ampullosporin displays narrow-spectrum antibacterial and antifungal activity, induces pigment formation by Phoma destructiva, causes hypothermia and decreased spontaneous locomotor activity in mice in dosages > 1 mg/kg.
Abstract: Ampullosporin (I; Ac-Trp-Ala-Aib-Aib-Leu-Aib-Gln-Aib-Aib-Aib-Gln-Leu-Aib-Gln-Leuol) was isolated from the mycelium of Sepedonium ampullosporum as a new 15-membered peptaibol-type antibiotic. The structure was determined by mass spectrometric and two-dimensional NMR experiments. Ampullosporin displays narrow-spectrum antibacterial and antifungal activity, induces pigment formation by Phoma destructiva, causes hypothermia and decreased spontaneous locomotor activity in mice in dosages > 1 mg/kg.
TL;DR: The novel 5,10-dihydrophencomycin methyl ester and the known microbial metabolites (2-hydroxyphenyl)-acetamide and menaquinone MK9 were isolated from an unidentified marine Streptomyces sp.
Abstract: The novel 5,10-dihydrophencomycin methyl ester (4) and the known microbial metabolites (2-hydroxyphenyl)-acetamide (1), menaquinone MK9 (II, III, VIII, IX-H8) (2), and phencomycin (3a) were isolated from an unidentified marine Streptomyces sp. and the structures were elucidated by NMR methods. Compound 4 shows weak antibiotic activity against Escherichia coli and Bacillus subtilis.
TL;DR: A related group of compounds belonging to the antimycin class of antibiotics was found in culture broth produced by a Streptomyces species and the structures of the new antimycins A7 and A8 were determined by spectroscopic analyses.
Abstract: A related group of compounds belonging to the antimycin class of antibiotics was found in culture broth produced by a Streptomyces species. The group includes known antimycins A1, A2, A3 and A4, and new antimycins A7 and A8. These compounds inhibit ATP-citrate lyase with Ki values of 4 to 60 μM against the substrate magnesium citrate. The structures of the new antimycins were determined by spectroscopic analyses.
TL;DR: 7d-decylaminomethyl derivative, whose minimal inhibitory concentrations for clinical isolates of staphylococci are 2 approximately 8 times lower than those of the parent antibiotic, was active against vancomycin-resistant VanA enterococci and Neisseria gonorrhoeae.
Abstract: A series of derivatives of eremomycin aminomethylated at the 7d position of the resorcinol ring of the amino acid No. 7 was prepared by interaction of eremomycin with formaldehyde and various primary and secondary amines and ammonia. The most active compound obtained was 7d-decylaminomethyl derivative, whose minimal inhibitory concentrations for clinical isolates of staphylococci are 2-8 times lower than those of the parent antibiotic. 7d-Decylaminomethyl derivative was also active against vancomycin-resistant VanA enterococci (8 μg/ml) and Neisseria gonorrhoeae (16 μg/ml).
TL;DR: Aflastatin A exhibits antimicrobial activity against some bacteria, yeasts and fungi as well as antitumor activity in aflatoxigenic fungi.
Abstract: Aflastatin A, a novel inhibitor of the production of aflatoxin by aflatoxigenic fungi, has been isolated from the solvent extract of mycelial cake of Streptomyces sp. and its molecular formula was determined as C62H115NO24. Aflastatin A completely inhibited aflatoxin production by Aspergillus parasiticus NRRL 2999 in liquid medium or on agar plate at a concentration of 0.5μg/ml. The mycelial growth of this fungus was not affected in the liquid medium at the same concentration, while the hyphal extension rate was reduced on the plate together with some morphological changes. The growth of the fungus was not completely inhibited even at a concentration of 100μg/ml. Aflastatin A exhibits antimicrobial activity against some bacteria, yeasts and fungi as well as antitumor activity.
TL;DR: Seven new phthalide compounds with anti-Helicobacter pylori activities were isolated from the basidiomycete Phanerochaete velutina CL6387, and the structure-activity relationship shows that the presence of a spiroketal part in addition to thephthalide part, greatly enhances the activity.
Abstract: Seven new phthalide compounds with anti-Helicobacter pylori activities were isolated from the basidiomycete Phanerochaete velutina CL6387. The two most potent phthalide compounds, CJ-12,954 and CJ-13,014, have MICs of 5 ng/ml. The structure-activity relationship shows that the presence of a spiroketal part in addition to the phthalide part, greatly enhances the activity. The phthalide compounds appear to be specific for H. pylori, since they did not show antibacterial activities when tested against a panel of other microorganisms.
TL;DR: The extract was chromatographed on a silica gel column using hexane EtOAcas eluting solvent and the activity (90mg) eluted with CHC13 175.
Abstract: with 300 ml of ^2-hexane. The water-alcohol fraction was extracted twice with 300ml of CH2C12and the active CH2C12 extracts concentrated to yield 600mg. The extract was chromatographed on a silica gel column using hexane EtOAcas eluting solvent. Fractions with antitumor activity (280 mg) were eluted with w-hexane EtOAc 75 : 25. Column chromatography on silica gel was repeated and the activity (90mg) eluted with CHC13 175
TL;DR: A new 32-membered macrolide antibiotic, brasilinolide A was isolated from the fermentation broth of Nocardia sp.
Abstract: A new 32-membered macrolide antibiotic, brasilinolide A was isolated from the fermentation broth of Nocardia sp. IFM 0406. The producer was identified as Nocardia brasiliensis. The antibiotic was only active against Aspergillus niger, but not active against other fungi including yeasts as well as other filamentous like fungi and bacteria. Brasilinolide A exerted an immunosuppressive activity in the assay system of a mixed lymphocyte reaction (MLR).
TL;DR: UK-2A and UK-3A are structural relatives of antimycins, which were isolated as antifungal antibiotics with little cytotoxicity that demonstrated inhibition of respiratory activity, and inhibition of rat liver respiration was thought to be the cytochrome bc1 complex in the mitochondrial electron transport chain of yeast cells.
Abstract: UK-2A and UK-3A are structural relatives of antimycins, which were isolated as antifungal antibiotics with little cytotoxicity that demonstrated inhibition of respiratory activity. They halve the cellular respiration of yeast within 4-5 minutes and the intracellular ATP content within 2-5 minutes. Moreover, they inhibited the yeast mitochondrial respiration using beta-hydroxybutyrate and succinate as a respiratory substrate, but no inhibition was observed using ascorbate-reduced tetramethyl p-phenylenediamine as the substrate. The site of respiratory inhibition of UK-2A and UK-3A was thought to be the cytochrome bc1 complex in the mitochondrial electron transport chain of yeast cells. They also inhibited the mitochondrial respiration of rat liver. It has been suggested that intact animal cells might have some system to defend themselves from the actions of UK-2A and UK-3A.
TL;DR: New apoptosis inducers derived from microorganisms are explored by utilizing a human promyelocytic leukaemia cell line, HL-60 as an indicator of apoptosis, and it is found that an actinomycete strain RK95-74 isolated from a soil sample collected in Shiki City, Saitama Prefecture, Japan, produced a new potent apoptosis inducer.
Abstract: response to various physiological or pathological stimuli. Apoptosis is involved in embryonic development, tissue remodeling, and tumor regression. Autoreactive T cells are selectively depleted by apoptosis during clonal selection in the immune system.2 ~4) Recently, it has been shownthat the efficacy of various anticancer agents is dependent on the intrinsic propensity of the target cells whether if the cells respond to the anticancer agents by apoptosis or not. In fact, apoptosis is induced by various anticancer agents such as cisplatin5), camptothecin6), etoposide7), and taxol8). The compounds which induced apoptosis in tumor cells might be a good candidate for anticancer drugs. From this point of view, we started to explore new apoptosis inducers derived from microorganisms by utilizing a human promyelocytic leukaemia cell line, HL-60 as an indicator ofapoptosis. In the course of our screening, we found that an actinomycete strain RK95-74 isolated from a soil sample collected in Shiki City, Saitama Prefecture, Japan, produced a new potent apoptosis inducer, cytotrienin A (1) containing a trieneansamycin, a 1-aminocyclopropane carboxylic acid and a 1-cyclohexene-l-carboxylic acid moieties. (Fig. 1). The strain RK95-74 was identified to be Streptomyces sp. and deposited in the National Institute of Bioscience APR. 1997
TL;DR: It has been postulated that AP-N performs multiple functions to regulate the action of hormones and neurotransmitters by inactivating such peptides at the cell surface by exploiting the hydrophobic domain of Zn2+dependent ectoenzyme.
Abstract: Aminopeptidase N [AP-N, EC 3.4.ll.2] is a Zn2+dependent ectoenzyme that is anchored in the plasma membranevia a hydrophobic domain adjacent to a small cytoplasmic region at the NH2terminus1'2). This enzyme is widely expressed by the brush border of the small intestine, synaptic cells of the central nervous system, and hematopoietic cells of myeloid lineage3). It has been postulated that AP-N performs multiple functions to regulate the action of hormonesand neurotransmitters by inactivating such peptides at the cell surface4'5).
TL;DR: The bacterium Pseudomonas aureofaciens 63-28 is antagonistic to several plant pathogenic fungi, including Pythium spp, and produced at least four antifungal metabolites active against Pythium ultimum and Phytophthora cryptogea when tested in culture for antIFungal activity.
Abstract: The bacterium Pseudomonas aureofaciens 63-28 is antagonistic to several plant pathogenic fungi, including Pythium spp. The bacterium produced at least four antifungal metabolites active against Pythium ultimum and Phytophthora cryptogea when tested in culture for antifungal activity. Two of these compounds were identified as the novel butyrolactones (Z)-4-hydroxy-4-methyl-2-(l-hexenyl)-2-butenolide and (Z)-4-hydroxymethyl-2-(l-hexenyl)-2-butenolide, by using NMR and GC-MS. All compounds were different from other antibiotics produced by Pseudomonas spp., including pyoluteorin, pyrrolnitrin, and 2, 4-diacetylphloroglucinol, as determined by HPLC. This is the first report of butyrolactones with antifungal activity produced by a saprophytic Pseudomonas spp.
TL;DR: Stachybotrin C and parvisporin, novel neuritogenic compounds, were isolated from the culture broth of Stachybotrys parvispora F4708 and induced significant neurite outgrowth in PC12 cells and showed cell survival activity in the primary culture of cerebral cortical neurons.
Abstract: Stachybotrin C and parvisporin, novel neuritogenic compounds, were isolated from the culture broth of Stachybotrys parvispora F4708. Stachybotrin C induced significant neurite outgrowth in PC12 cells and showed cell survival activity in the primary culture of cerebral cortical neurons. Parvisporin demonstrated only weak neuritogenic activity.