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1.
J Nat Prod ; 79(9): 2167-74, 2016 09 23.
Article in English | MEDLINE | ID: mdl-27626956

ABSTRACT

Seven novel spiromeroterpenoids, asnovolins A-G (1-7), one of which was shown to suppress fibronectin expression, were isolated from Aspergillus novofumigatus CBS117520 along with a known compound, novofumigatonin (8). The structures of asnovolins A-G were elucidated using MS and 2D-NMR data. Asnovolin E (5) suppressed fibronectin expression by normal human neonatal dermal fibroblast cells.


Subject(s)
Spiro Compounds/isolation & purification , Spiro Compounds/pharmacology , Terpenes/isolation & purification , Terpenes/pharmacology , Aspergillus/chemistry , Drug Screening Assays, Antitumor , Fibronectins , Humans , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Spiro Compounds/chemistry , Terpenes/chemistry
2.
J Antibiot (Tokyo) ; 69(2): 89-96, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26306816

ABSTRACT

Three new phthalide derivatives, emefuranones A1, A2 and B (1-3); six new phthalane derivatives, emefuran A, B1, B2, C1, C2 and D (4-9); three new farnesylated phthalide derivatives, farnesylemefuranones A-C (10-12); xylarinol C (13); and emericelloxide (14), along with four known compounds (dustanin, sorbicillin, aspergillodiol and xylarinol A), were isolated from the culture extracts of Emericella sp. IFM57991. Structures of 1-14 were elucidated on the basis of spectroscopic analysis and chemical evidence. Compounds 4-7 and 13 showed moderate antibacterial activities against Bacillus subtilis.


Subject(s)
Anti-Infective Agents/pharmacology , Bacillus subtilis/drug effects , Benzofurans/pharmacology , Culture Media/chemistry , Emericella/metabolism , Phthalimides/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/isolation & purification , Benzofurans/chemistry , Benzofurans/isolation & purification , Disk Diffusion Antimicrobial Tests , Emericella/growth & development , Humans , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Structure , Phthalimides/chemistry , Phthalimides/isolation & purification
3.
Eukaryot Cell ; 13(11): 1380-92, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25172766

ABSTRACT

The peptide transporter Ptr2 plays a central role in di- or tripeptide import in Saccharomyces cerevisiae. Although PTR2 transcription has been extensively analyzed in terms of upregulation by the Ubr1-Cup9 circuit, the structural and functional information for this transporter is limited. Here we identified 14 amino acid residues required for peptide import through Ptr2 based on the crystallographic information of Streptococcus thermophilus peptide transporter PepTst and based on the conservation of primary sequences among the proton-dependent oligopeptide transporters (POTs). Expression of Ptr2 carrying one of the 14 mutations of which the corresponding residues of PepTst are involved in peptide recognition, salt bridge interaction, or peptide translocation failed to enable ptr2Δtrp1 cell growth in alanyl-tryptophan (Ala-Trp) medium. We observed that Ptr2 underwent rapid degradation after cycloheximide treatment (half-life, approximately 1 h), and this degradation depended on Rsp5 ubiquitin ligase. The ubiquitination of Ptr2 most likely occurs at the N-terminal lysines 16, 27, and 34. Simultaneous substitution of arginine for the three lysines fully prevented Ptr2 degradation. Ptr2 mutants of the presumed peptide-binding site (E92Q, R93K, K205R, W362L, and E480D) exhibited severe defects in peptide import and were subjected to Rsp5-dependent degradation when cells were moved to Ala-Trp medium, whereas, similar to what occurs in the wild-type Ptr2, mutant proteins of the intracellular gate were upregulated. These results suggest that Ptr2 undergoes quality control and the defects in peptide binding and the concomitant conformational change render Ptr2 subject to efficient ubiquitination and subsequent degradation.


Subject(s)
Binding Sites/genetics , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Protein Transport/genetics , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/genetics , Amino Acid Sequence , Carrier Proteins/genetics , Crystallography, X-Ray , Cycloheximide/pharmacology , Endosomal Sorting Complexes Required for Transport/metabolism , Membrane Transport Proteins/ultrastructure , Protein Synthesis Inhibitors/pharmacology , Saccharomyces cerevisiae/growth & development , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/ultrastructure , Streptococcus thermophilus/genetics , Streptococcus thermophilus/metabolism , Ubiquitin/metabolism , Ubiquitin-Protein Ligase Complexes/metabolism , Ubiquitination
5.
J Nat Prod ; 76(11): 2034-9, 2013 Nov 22.
Article in English | MEDLINE | ID: mdl-24262004

ABSTRACT

A proposed structure for schizocommunin (Z)-1(hydroxy) and its geometric isomer (E)-1(hydroxy), which exist in a keto form, has been synthesized. However, the spectroscopic data of (Z)-1(keto) and (E)-1(keto) were not consistent with those reported for natural schizocommunin. After reinvestigating the spectral data for natural schizocommunin, we synthesized the quinazolinone derivative (Z)-2 as a revised structure for schizocommunin. All of the spectral data of (Z)-2 were completely identical to those reported for natural schizocommunin. (Z)-2 showed moderate antiproliferative activity.


Subject(s)
Indoles/chemistry , Indoles/chemical synthesis , Drug Screening Assays, Antitumor , HeLa Cells , Humans , Indoles/pharmacology , Molecular Structure , Stereoisomerism , Structure-Activity Relationship
6.
Sci Pharm ; 79(4): 937-50, 2011.
Article in English | MEDLINE | ID: mdl-22145116

ABSTRACT

Three new quinazolinobenzodiazepine derivatives, novobenzomalvins A (1), B (2), and C (3), have been isolated as fibronectin expression regulators from Aspergillus novofumigatus CBS117520. The structures of 1 to 3 were established by spectroscopic and physicochemical analysis, and chemical investigation including the total synthesis of 1. Treatment with novo-benzomalvins A (1), B (2), C (3), and N-methylnovobenzomalvin A (5) increased the expression of fibronectin in normal human neonatal dermal fibroblast cells.

8.
Chem Pharm Bull (Tokyo) ; 58(5): 717-9, 2010 May.
Article in English | MEDLINE | ID: mdl-20460802

ABSTRACT

Two new diketopiperazine metabolites, novoamauromine (1) and ent-cycloechinulin (2) have been isolated from Aspergillus novofumigatus CBS117520. The structures of 1 and 2 were established on the basis of spectroscopic and chemical investigation, including a detailed comparison of the spectroscopic and physico-chemical data of amauromine (3) and cycloechinulin (4).


Subject(s)
Antifungal Agents , Antineoplastic Agents , Aspergillus/chemistry , Diketopiperazines/chemistry , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Chromatography, Liquid , Fungi/drug effects , Humans , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Molecular Structure
10.
J Nat Med ; 63(1): 96-9, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18850072

ABSTRACT

In a screen searching for new bioactive agents, a new indoloditerpene, penijanthine A (1), was isolated from Penicillium janthinellum IFM 55557. The structure of 1 was established on the basis of spectroscopic and chemical investigation, as well as detailed comparison with the spectroscopic and physico-chemical data of paxilline (2), which was isolated along with 1.


Subject(s)
Diterpenes/chemistry , Diterpenes/isolation & purification , Indoles/chemistry , Penicillium/chemistry , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Antifungal Agents/pharmacology , Aspergillus fumigatus/drug effects , Diterpenes/pharmacology , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Molecular Structure
11.
J Nat Prod ; 71(9): 1640-2, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18771240

ABSTRACT

In the course of searching for new antifungal agents, a new cyclic depsipeptide, eujavanicin A (1), was isolated from Eupenicillium javanicum as an antifungal agent against the human pathogenic filamentous fungus Aspergillus fumigatus. The structure of 1 was established by spectroscopic and chemical investigations. The absolute stereochemistry was elucidated by Marfey's method and by chiral HPLC analysis.


Subject(s)
Antifungal Agents/isolation & purification , Antifungal Agents/pharmacology , Aspergillus fumigatus/drug effects , Depsipeptides/isolation & purification , Depsipeptides/pharmacology , Antifungal Agents/chemistry , Bacillus subtilis/drug effects , Depsipeptides/chemistry , Escherichia coli/drug effects , Humans , Japan , Microbial Sensitivity Tests , Molecular Structure , Salmonella enteritidis/drug effects , Staphylococcus aureus/drug effects
12.
J Nat Med ; 62(3): 384-6, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18409064

ABSTRACT

Fifteen derivatives of falconensin were examined for their inhibitory activity against the induction of ear edema in mouse ear by application of 12-O-tetradecanoylphorbol-13-acetate (TPA). It was demonstrated that azaphilonoid falconensins exert inhibitory effects against TPA-induced inflammation in the ears of mice to a comparable degree as moascorubrin and indomethacin, which are known to have antitumor-promoting and anti-inflammatory effects. All compounds tested, except monomethylmitorubrin, inhibited the inflammatory activity induced by TPA.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Benzopyrans/pharmacology , Emericella/chemistry , Inflammation/drug therapy , Pigments, Biological/pharmacology , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Benzopyrans/chemistry , Benzopyrans/isolation & purification , Disease Models, Animal , Ear/pathology , Edema/chemically induced , Edema/drug therapy , Female , Indomethacin/pharmacology , Inflammation/chemically induced , Mice , Mice, Inbred ICR , Pigments, Biological/chemistry , Pigments, Biological/isolation & purification , Structure-Activity Relationship , Tetradecanoylphorbol Acetate/toxicity
13.
Pulm Pharmacol Ther ; 21(2): 356-9, 2008.
Article in English | MEDLINE | ID: mdl-17951087

ABSTRACT

We examined the sensitivity of the cough reflex to inhaled citric acid in guinea pigs that had been actively sensitized with the protein fraction of Aspergillus restrictus strain A-17. The number of coughs elicited by an aerosol of 5% citric acid was significantly increased in the sensitized group compared to the non-sensitized group. The number of citric-acid-induced coughs in sensitized guinea pigs was dose-dependently and significantly reduced to the level in non-sensitized guinea pigs when animals were pretreated with fexofenadine, a selective histamine H1 receptor antagonist, 60min before citric acid inhalation. The bronchial responsiveness to inhaled methacholine or histamine in the sensitized group was not significantly heightened compared to the non-sensitized group. These results suggest that active sensitization with the protein fraction of A. restrictus by itself, that is without subsequent allergen challenge, enhances the excitability of cough receptors to tussive stimuli, and the physiologic features of this animal model are consistent with those of atopic cough.


Subject(s)
Antigens, Fungal/immunology , Aspergillus/immunology , Cough/immunology , Fungal Proteins/immunology , Respiratory Hypersensitivity/immunology , Administration, Inhalation , Animals , Antitussive Agents/administration & dosage , Antitussive Agents/pharmacology , Bronchial Hyperreactivity/chemically induced , Bronchial Hyperreactivity/immunology , Bronchial Hyperreactivity/physiopathology , Bronchoconstrictor Agents/administration & dosage , Bronchoconstrictor Agents/pharmacology , Citric Acid , Cough/chemically induced , Cough/physiopathology , Dose-Response Relationship, Drug , Guinea Pigs , Histamine/administration & dosage , Histamine/pharmacology , Histamine Agonists/administration & dosage , Histamine Agonists/pharmacology , Histamine H1 Antagonists, Non-Sedating/administration & dosage , Histamine H1 Antagonists, Non-Sedating/pharmacology , Male , Methacholine Chloride/administration & dosage , Methacholine Chloride/pharmacology , Respiratory Hypersensitivity/chemically induced , Respiratory Hypersensitivity/physiopathology , Terfenadine/administration & dosage , Terfenadine/analogs & derivatives , Terfenadine/pharmacology
14.
J Nat Prod ; 70(9): 1510-2, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17711347

ABSTRACT

Three new decalin derivatives, eujavanicols A-C (1-3), were isolated from an extract of Eupenicillium javanicum IFM 54704. Their structures were determined by chemical and spectroscopic methods.


Subject(s)
Eurotiales/chemistry , Naphthalenes/chemistry , Naphthalenes/isolation & purification , Japan , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular
15.
J Antibiot (Tokyo) ; 60(6): 388-90, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17617697

ABSTRACT

In the course of screening for hyaluronidase (HAase) inhibitory agents, a new gamma-pyrone derivative, lepidepyrone, C(8)H(10)O(5), was isolated from the cultured mycelium of the mushroom Neolentinus lepideus TMC-1102 as a major HAase inhibitory compound (IC(50) 3.3 mM). The structure of lepidepyrone was established on the basis of spectroscopic investigation.


Subject(s)
Basidiomycota/chemistry , Enzyme Inhibitors/isolation & purification , Hyaluronoglucosaminidase/antagonists & inhibitors , Pyrones/isolation & purification , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/metabolism , Enzyme Inhibitors/pharmacology , Hyaluronoglucosaminidase/metabolism , Inhibitory Concentration 50 , Mass Spectrometry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Pyrones/chemistry , Pyrones/metabolism , Pyrones/pharmacology , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet
16.
J Reconstr Microsurg ; 23(3): 163-71, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17479455

ABSTRACT

The treatment of neuroma-in-continuity is controversial. To bypass neuroma-in-continuity with a nerve graft using end-to-side neurorrhaphy is considered to be theoretically a good option. To test this therapeutic modality, we performed a nerve bypass graft in a neuroma-in-continuity rat model. An obstructive neuroma-in-continuity was created in a transected peroneal nerve by interposition using the aponeurosis of the spinal muscles. In the experimental animals, (1) immediate, (2) 3-week delayed, or (3) no ulnar nerve bypass graft was performed. The peroneal functional index (PFI), conduction velocity, tibialis anterior muscle weight, and histomorphometric analyses were performed and compared with control (simply cut and repair) animals. On postoperative day 70, the recoveries of the PFI values, conduction velocity, and tibialis anterior muscle weight in the bypassed animals showed no significant differences as compared with the control animals, and the extent of these recoveries in the bypassed animals were significantly superior to those in the no-graft animals. In the histomorphometric analysis, the mean percent nerve in the bypassed animals was significantly larger than that in the no-graft animals. In conclusion, this technique may be a good alternative to the current therapeutic techniques for neuroma-in-continuity when there is a significant retained function.


Subject(s)
Neuroma/surgery , Peripheral Nervous System Neoplasms/surgery , Peroneal Nerve/surgery , Ulnar Nerve/transplantation , Animals , Disease Models, Animal , Male , Muscle, Skeletal/pathology , Nerve Fibers/ultrastructure , Neural Conduction , Organ Size , Rats , Rats, Sprague-Dawley , Walking
17.
Arerugi ; 56(2): 101-8, 2007 Feb.
Article in Japanese | MEDLINE | ID: mdl-17347596

ABSTRACT

BACKGROUND AND PURPOSE: The typical xerophilic fungi, Aspergillus restrictus, have been very frequently detected in house dust by low water activity medium. Since the composition of fungal allergens are affected culture and extract condition, we considered the influence in A. restrictus in order to develop new allergen of xerophilic fungi. METHOD: The 4 different extract of A. restrictus were obtained from various fermentation and extraction methods. These extracts were studied for specific IgE in sera of patients with asthma. The cross-reactivity between A. restrictus and A. fumigatus were analyzed by enzyme-linked immunosorbent assay (ELISA) inhibition. Then, component analysis of A. restrictus allergens was examined by SDS-PAGE and Western Blotting. RESULT: In ELISA, IgE antibodies against four extracts of A. restrictus were found in sera of 20-48%. In ELISA inhibition using sera obtained from 11 asthma patients, A. fumigatus antigen solution inhibited the reaction of A. restrictus with 5 asthma patients. CONCLUSION: These results indicated that A. restrictus may be important as a causative agent in adult asthma patients. However, it was suggested that some preparation methods of an extract influence activity. Furthermore, cross-reactivity was found between A. restrictus and A. fumigatus.


Subject(s)
Allergens/immunology , Aspergillus/immunology , Asthma/immunology , Fungi/immunology , Adult , Allergens/isolation & purification , Electrophoresis, Polyacrylamide Gel , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin E
18.
Chem Pharm Bull (Tokyo) ; 54(12): 1639-41, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17139096

ABSTRACT

In the course of searching for bioactive substances, two new dioxopiperazine derivatives, arestrictins A (1) and B (2), were isolated along with the known dioxopiperazine, cristatin A (3), and the known peptide, asperglucide (4), from the organic extract of the xerophilic fungi, Aspergillus restrictus and Aspergillus penicilloides. The absolute structures of 1 and 2, except for the configuration of the secondary alcohol in 1, were established by spectroscopic and chemical investigation. The absolute configuration of cristatin A (3) was also determined.


Subject(s)
Aspergillus/chemistry , Piperazines/chemistry , Tryptophan/analogs & derivatives , Molecular Structure , Piperazine , Tryptophan/chemistry
19.
J Antibiot (Tokyo) ; 59(9): 597-600, 2006 Sep.
Article in English | MEDLINE | ID: mdl-17136892

ABSTRACT

In screening for antifungal substances, a new macrolide, eushearilide (1), was isolated from Eupenicillium shearii IFM54447. The structure of 1 was established to be 24-membered macrolide having a non-conjugated diene and a choline phosphate ester moetiy on the basis of detailed investigation of NMR, UV, IR and MS spectral data. Compound 1 showed antifungal activity against various fungi and yeasts, including human pathogens Aspergillus fumigatus, Trichophyton spp. and Candida spp.


Subject(s)
Antifungal Agents/isolation & purification , Antifungal Agents/pharmacology , Eurotiales/metabolism , Macrolides/isolation & purification , Macrolides/pharmacology , Phosphorylcholine/analogs & derivatives , Antifungal Agents/chemistry , Aspergillus fumigatus/drug effects , Candida/drug effects , Macrolides/chemistry , Microbial Sensitivity Tests , Molecular Structure , Phosphorylcholine/chemistry , Phosphorylcholine/isolation & purification , Phosphorylcholine/pharmacology , Spectrum Analysis , Trichophyton/drug effects
20.
Org Lett ; 8(24): 5589-92, 2006 Nov 23.
Article in English | MEDLINE | ID: mdl-17107079

ABSTRACT

Arabidopsis thaliana LUP1 (At1g78970) catalyzes the cyclization of oxidosqualene into lupeol and 3beta,20-dihydroxylupane (lupanediol). The stereochemical course of water addition to the lupanyl cation was studied. The X-ray crystal structure of lupanylepoxide 3,5-dinitrobenzoate established the configuration of epoxide as 20S. LiAlD4 reduction of the epoxide enabled the chemical shift assignment of prochiral methyl groups at C20 of lupanediol. Correlation of these methyl groups with biosynthetic lupanediol from [1,2-(13)C(2)] acetate established the stereochemical course of water addition. [reaction: see text].


Subject(s)
Arabidopsis Proteins/chemistry , Intramolecular Transferases/chemistry , Triterpenes/chemical synthesis , Crystallography, X-Ray , Cyclization , Magnetic Resonance Spectroscopy , Molecular Conformation , Oxidation-Reduction , Stereoisomerism , Water/chemistry
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