ABSTRACT
Structures of the new aminocyclitol antibiotics, inosamycins A, B, C, D and E, have been determined by a combination of chemical degradation and spectroscopic studies. They are structurally related to neomycin, paromomycin and ribostamycin but differ in that all the inosamycin components contain 2-deoxy-scyllo-inosamine in place of 2-deoxystreptamine in the known aminoglycoside antibiotics.
Subject(s)
Anti-Bacterial Agents , Aminoglycosides/biosynthesis , Anti-Bacterial Agents/biosynthesis , Chemical Phenomena , Chemistry , Magnetic Resonance SpectroscopyABSTRACT
An unidentified oligosporic actinomycete strain, No. E864-61, produced two new antibiotics, Bu-2313 A (C27H35NO9) and Bu-2313 B (C26H33NO9). Bu-2313 A and B each exhibited a broad antibiotic spectrum against Gram-positive and Gram-negative anaerobic bacteria, and showed in vivo activity against experimental infections produced by B. fragilis and C. perfringens. Bu-2313 also inhibited some aerobic bacteria such as streptococci. Bu-2313 B was approximately two-fold more active than Bu-2313 A.
Subject(s)
Aminoglycosides , Anti-Bacterial Agents/pharmacology , Actinomycetales/metabolism , Anaerobiosis , Animals , Anti-Bacterial Agents/analogs & derivatives , Anti-Bacterial Agents/biosynthesis , Anti-Bacterial Agents/isolation & purification , Bacteria/drug effects , Bacterial Infections/drug therapy , Chemical Phenomena , Chemistry, Physical , Lethal Dose 50 , MiceABSTRACT
The structures of Bu-2313 A and B have been determined. They are dienoyltetramic acid-containing antibiotics structurally related to streptolydigin and tirandamycin.
Subject(s)
Aminoglycosides , Anti-Bacterial Agents , Anti-Bacterial Agents/analogs & derivatives , Chemical Phenomena , Chemistry , Hydrolysis , Magnetic Resonance Spectroscopy , Mass Spectrometry , Oxidation-Reduction , Spectrophotometry, UltravioletABSTRACT
A new antitumor antibiotic porothramycin was produced by a new strain of Streptomyces albus. The antibiotic was isolated in two active forms, the natural free hydroxyl form (porothramycin A) or the crystalline methyl ether form (porothramycin B) depending upon the isolation process used. Structural studies established that porothramycin is a new member of the pyrrolo[1,4]benzodiazepine group antibiotics having only one substituent on the benzene ring. The antibiotic exhibited antimicrobial activity against Gram-positive bacteria and anaerobes and significantly prolonged the survival times of mice implanted with experimental tumors.
Subject(s)
Anthramycin/isolation & purification , Antibiotics, Antineoplastic/isolation & purification , Benzodiazepinones/isolation & purification , Animals , Anthramycin/analogs & derivatives , Anthramycin/pharmacology , Antibiotics, Antineoplastic/pharmacology , Chemical Phenomena , Chemistry , Gram-Positive Bacteria/drug effects , Hydrolysis , Leukemia L1210/drug therapy , Leukemia P388/drug therapy , Magnetic Resonance Spectroscopy , Melanoma, Experimental/drug therapy , Mice , Microbial Sensitivity Tests , Streptomyces/metabolismABSTRACT
A novel aminoglycoside antibiotic, boholmycin, was produced by Streptomyces hygroscopicus H617-25 isolated from a soil sample collected in Bohol Island, the Philippines. It has a pseudotetrasaccharide structure composed of a heptose, two aminosugars and dicarbamoyl-scyllo-inositol. Intrinsic antibacterial activity of boholmycin is weak but it exhibits broad spectrum activity against Gram-positive and Gram-negative bacteria including aminoglycoside-resistant strains. Boholmycin is non-toxic in mice at 1,000 mg/kg intravenously.
Subject(s)
Aminoglycosides , Anti-Bacterial Agents/isolation & purification , Streptomyces/metabolism , Animals , Anti-Bacterial Agents/biosynthesis , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Chemical Phenomena , Chemistry , Fermentation , MiceABSTRACT
The structures of novel antiviral antibiotics, cycloviracins B1 and B2 have been determined by means of chemical and spectroscopic methods including 2D NMR correlation spectroscopy. The antibiotics are unique macrocyclic diesters consisting of two D-glucoses, three 2-O-methyl-D-glucoses and two (C24 and C26) hydroxy fatty acids.
Subject(s)
Actinomycetales/chemistry , Anti-Bacterial Agents/chemistry , Antiviral Agents/chemistry , Macrolides , Antiviral Agents/isolation & purification , Hydrolysis , Magnetic Resonance SpectroscopyABSTRACT
Kibdelosporangium albatum No. R761-7 (ATCC 55061) produced new antiviral antibiotics, cycloviracins B1 and B2. They show weak activity against Gram-positive bacteria and potent antiviral activity against herpes simplex virus type 1. Unique acylsaccharide structures were established for cycloviracins B1 and B2 by degradation and spectroscopic analysis.
Subject(s)
Actinomycetales/chemistry , Anti-Bacterial Agents/isolation & purification , Antiviral Agents/isolation & purification , Macrolides , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Simplexvirus/drug effectsABSTRACT
A strain of Amycolatopsis orientalis No. Q427-8 (ATCC 53884) was found to produce a complex of new antiviral antibiotics, quartromicin which consisted of at least six components A1, A2, A3, D1, D2 and D3. Structural studies suggested that they are a novel type of molecules unrelated to any known antibiotics. Each component of quartromicin exhibited antiviral activity against herpes simplex virus type 1, influenza virus type A and human immunodeficiency virus.
Subject(s)
Actinomycetales/classification , Antiviral Agents/isolation & purification , Orthomyxoviridae/drug effects , Simplexvirus/drug effects , Actinomycetales/metabolism , Animals , Antiviral Agents/chemistry , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Chemical Phenomena , Chemistry, Physical , Fermentation , Lactones/chemistry , Lactones/isolation & purification , Lactones/metabolism , Lactones/pharmacology , Magnetic Resonance Spectroscopy , Spiro Compounds/chemistry , Spiro Compounds/isolation & purification , Spiro Compounds/metabolism , Spiro Compounds/pharmacology , Vero CellsABSTRACT
Melanostatin, a new antibiotic with melanin synthesis inhibitor activity, was isolated from the fermentation broth of Streptomyces clavifer No. N924-2. Its structure was determined by spectral analysis and degradation experiments. Melanostatin strongly inhibited melanin formation in Streptomyces bikiniensis NRRL B-1049 and B16 melanoma cells.
Subject(s)
MSH Release-Inhibiting Hormone/biosynthesis , Melanins/antagonists & inhibitors , Streptomyces/classification , Chromatography, Thin Layer , Fermentation , MSH Release-Inhibiting Hormone/chemistry , MSH Release-Inhibiting Hormone/isolation & purification , MSH Release-Inhibiting Hormone/pharmacology , Magnetic Resonance Spectroscopy , Melanins/biosynthesis , Melanoma, Experimental , Microscopy, Electron, Scanning , Molecular Structure , Monophenol Monooxygenase/antagonists & inhibitors , Soil Microbiology , Solubility , Spectrophotometry, Infrared , Streptomyces/drug effects , Streptomyces/metabolism , Streptomyces/ultrastructure , Tumor Cells, CulturedABSTRACT
A strain of Streptomyces hygroscopicus No. J296-21 (ATCC 39150) was found to produce a complex of new antibiotics, called inosamycins, which consisted of components A, B, C, D and E. They are novel aminocyclitol antibiotics structurally related to neomycin, paromomycin and ribostamycin. The antibiotic complex and each component of inosamycin exhibit a broad antibacterial spectrum but they are inactive against most of the aminoglycoside-resistant organisms. The antibacterial activity of inosamycin A, the major component of the complex, is comparable to that of neomycin but its acute toxicity is significantly lower (ca. 1/3) than that of neomycin.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Aminoglycosides/isolation & purification , Aminoglycosides/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/toxicity , Bacteria/drug effects , Bacterial Infections/drug therapy , Chemical Phenomena , Chemistry , Fermentation , Mice , Streptomyces/classification , Streptomyces/metabolismSubject(s)
Bacillus/growth & development , Dipeptides/isolation & purification , Leucyl Aminopeptidase/antagonists & inhibitors , Animals , Bacillus/classification , Chemical Phenomena , Chemistry , Culture Media , Dipeptides/pharmacology , Kidney/enzymology , Kinetics , Magnetic Resonance Spectroscopy , Mass Spectrometry , Rabbits , Spectrophotometry, Ultraviolet , Substrate Specificity , SwineSubject(s)
Anti-Bacterial Agents/biosynthesis , Lincomycin/analogs & derivatives , Animals , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Bacterial Infections/drug therapy , Fermentation , Lincomycin/analysis , Lincomycin/biosynthesis , Lincomycin/pharmacology , Mice , Streptomyces/metabolismSubject(s)
Anthracyclines , Antibiotics, Antineoplastic/isolation & purification , Antifungal Agents/isolation & purification , Animals , Antibiotics, Antineoplastic/pharmacology , Antifungal Agents/pharmacology , Chemical Phenomena , Chemistry , Mice , Microbial Sensitivity Tests , Nocardia/metabolismSubject(s)
Antibiotics, Antineoplastic/isolation & purification , Antifungal Agents/isolation & purification , Animals , Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Butadienes/chemistry , Butadienes/isolation & purification , Butadienes/pharmacology , Fermentation , Humans , Melanoma, Experimental/drug therapy , Mice , Microbial Sensitivity Tests , Nitriles/chemistry , Nitriles/isolation & purification , Nitriles/pharmacology , Tumor Cells, Cultured/drug effectsSubject(s)
Anti-Bacterial Agents/chemistry , Antiviral Agents/chemistry , Peptides , Amino Acid Sequence , Anti-Bacterial Agents/pharmacology , Antiviral Agents/pharmacology , HIV-1/drug effects , Intercellular Signaling Peptides and Proteins , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Sequence Data , Molecular StructureSubject(s)
Anti-Bacterial Agents/isolation & purification , Antiviral Agents/isolation & purification , Peptides , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Fermentation , Intercellular Signaling Peptides and Proteins , Microbial Sensitivity Tests , Protein Conformation , StreptomycesABSTRACT
Low-level chemiluminescence is produced in a hydrogen peroxide (H(2)O(2))/gallic acid/haemoprotein system with single broad peaks around 520 nm, regardless of the biological role of the haemoprotein. The free haem iron systems (haemin and haematin systems) gave a higher photon intensity (1.5 x 10(4) and 2.0 x 10(4) cps) than that of the H(2)O(2)/gallic acid/haematoporphyrin system. These results indicated that haem iron plays a significant role in the photon emission of haemoprotein systems. A free radical with a g value of 2. 0058 was detected through a direct electron spin resonance (ESR) method. The photon intensity of the H(2)O(2)/gallic acid/haemoprotein system decreased in the order: HRP > cytochrome c > myoglobin > haemoglobin, and this corresponded to the decrease in radical intensity. These results indicated that the formation of the free radical with a g value of 2.0058 may be the key step for chemiluminescence in the H(2)O(2)/gallic acid/haemoprotein system. A quartet line similar to DMPO-OH adducts and uncomplexed free radicals (g = 2.0058) was detected using the ESR spin-trapping method in the H(2)O(2)/gallic acid/cytochrome c system.
Subject(s)
Electron Spin Resonance Spectroscopy/methods , Free Radicals/analysis , Gallic Acid/chemistry , Hemeproteins/chemistry , Hydrogen Peroxide/chemistry , Hemin/chemistry , Hemoglobins/chemistry , Luminescent Measurements , Myoglobin/chemistryABSTRACT
The 21-amino acid peptides siamycin II (BMY-29303) and siamycin I (BMY-29304), derived from Streptomyces strains AA3891 and AA6532, respectively, have been found to inhibit HIV-1 fusion and viral replication in cell culture. The primary sequence of siamycin II is CLGIGSCNDFAGCGYAIVCFW. Siamycin I differs by only one amino acid; it has a valine residue at position 4. In both peptides, disulfide bonds link Cys1 with Cys13 and Cys7 with Cys19, and the side chain of Asp9 forms an amide bond with the N-terminus. Siamycin II, when dissolved in a 50:50 mixture of DMSO and H2O, yields NOESY spectra with exceptional numbers of cross peaks for a peptide of this size. We have used 335 NOE distance constraints and 13 dihedral angle constraints to generate an ensemble of 30 siamycin II structures; these have average backbone atom and all heavy atom rmsd values to the mean coordinates of 0.24 and 0.52 A, respectively. The peptide displays an unusual wedge-shaped structure, with one face being predominantly hydrophobic and the other being predominantly hydrophilic. Chemical shift and NOE data show that the siamycin I structure is essentially identical to siamycin II. These peptides may act by preventing oligomerization of the HIV transmembrane glycoprotein gp41, or by interfering with interactions between gp41 and the envelope glycoprotein gp120, the cell membrane or membrane-bound proteins [Frèchet, D. et al. (1994) Biochemistry, 33, 42-50]. The amphipathic nature of siamycin II and siamycin I suggests that a polar (or apolar) site on the target protein may be masked by the apolar (or polar) face of the peptide upon peptide/protein complexation.