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US 7,407,654 B2Granted
Antibiotics GE 81112 factors A,B,B1, pharmaceutically acceptable salts and compositions, and use thereof
AssigneeVicuron Pharmaceuticals Inc.
InventorsEnrico Selva, Flavia Marinelli, Daniele Losi, Linda Cavaletti, Ameriga Lazzarini, Alessandra Marazzi
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Abstract
The invention relates to an antibiotic substances of microbial origin, arbitrarily denominated antibiotic GE 81112 factor A, factor B1 and factor B, which is produced by fermentation of Streptomyces sp. DSMZ 14386, the pharmaceutically acceptable salts and compositions thereof, and their use as an antibacterial agent having inhibitory activity versus susceptible microbes.
Claims18
An isolated antibiotic GE 81112 Factor A comprising the following characteristics:
- A) Mass spectrum recorded from a 0.01 mg/ml solution in acetonitrile:
- water 50:50 giving a monoprotonated ion at 644 m/z on a Thermofinnigan® LCQ deca mass spectrum instrument under the following electrospray conditions:
- Spray Voltage:
- 4.7 kV;
- Capillary temperature:
- 250° C.;
- Capillary Voltage 9V;
- Infusion mode 5 μl/min;
- B) Infrared Spectrum recorded as a nujol mull with an IFS-48® Fourier Transform infrared spectrophotometer showing the following main bands (cm−1):
- 3356;
- 2956;
- 2855;
- 2256;
- 2128;
- 1663;
- 1596;
- 1455;
- 1378;
- 1345;
- 1123;
- 1050;
- 1026;
- 1002;
- 825;
- 764;
- C) 1H-NMR spectrum recorded at 600 MHz at 25° C. in DMSO-d6, comprising at least one drop of trifluoroacetic acid, showing the following 1H signals:
- Chemical Shift (ppm)
- Multiplicity
- 1.52
- br d
- 1.57-1.67
- m
- 1.81
- br d
- 1.88
- m
- 2.87
- dd
- 2.90
- m
- 3.12
- dd
- 3.15
- m
- 3.65
- m
- 3.83
- m
- 3.94
- br d
- 4.40
- br s
- 4.46
- m
- 4.50
- dd
- 4.70
- M
- 5.06
- D
- 6.46
- Br
- 6.94
- S
- 7.29
- S
- 7.99
- D
- 8.17
- D
- 8.30
- M
- 8.57
- br d
- 8.95
- D
- 9.06
- br d
- 14.09
- Br
- 14.27
- Br
- —
- —
- D) 13C-NMR spectrum recorded at 150 MHz, at 25° C. in DMSO-d6, comprising at least one drop of trifluoroacetic acid, showing the following 13C signals
- Chemical Shift (ppm)
- Multiplicity
- 15.9
- t
- 27.19
- t
- 28.14
- t
- 35.31
- t
- 42.86
- t
- 50.13
- d
- 51.30
- d
- 56.86
- d
- 59.71
- d
- 64.07
- d
- 65.11
- d
- 66.88
- d
- 67.76
- T
- 116.83
- d
- 118.49
- d
- 128.41
- s
- 129.03
- s
- 133.65
- d
- 139.66
- s
- 156.73
- s
- 167.39
- s
- 170.16
- s
- 171.29
- s
- 171.65
- s
- E) Retention time 14.1 min, determined by using an analytical HPLC pump Shimadzu® LC10-AS equipped with a chromatographic column Altima® RP18, 5 μm, 250×4.6 mm i.d column;
- isocratic elution performed at 1 ml/min. flow rate, with 40 mM ammonium formate buffer, brought to pH 4.5 by addition of formic acid;
- UV detection at 230 nm;
- F) possesses acid functions and basic functions;
- and
- G) inhibits the growth of Moraxella catarrhalis;
- inhibits the growth of Escherichia coli and Bacillus subtilis when these bacteria are cultivated in minimal media;
- shows marginal activity against Streptococcus pneumoniae;
- does not inhibit growth of Candida albicans, and
- wherein the antibiotic GE 81112 Factor A also includes one or more corresponding salts formed with acids and/or bases.
142 more elements
An isolated antibiotic mixture comprising antibiotic GE 81112 Factor A comprising the following characteristics:
- A) Mass spectrum recorded from a 0.01 mg/ml solution in acetonitrile:
- water 50:50 giving a monoprotonated ion at 644 m/z on a Thermofinnigan® LCQ deca mass spectrum instrument under the following electrospray conditions:
- Spray Voltage:
- 4.7 kV;
- Capillary temperature:
- 250° C.;
- Capillary Voltage 9V;
- Infusion mode 5 μl/min;
- B) Infrared Spectrum recorded as a nujol mull with an IFS-48® Fourier Transform infrared spectrophotometer showing the following main bands (cm−1):
- 3356;
- 2956;
- 2855;
- 2256;
- 2128;
- 1663;
- 1596;
- 1455;
- 1378;
- 1345;
- 1123;
- 1050;
- 1026;
- 1002;
- 825;
- 764;
- C) 1H-NMR spectrum recorded at 600 MHz at 25° C. in DMSO-d6 comprising at least one drop of trifluoroacetic acid showing the following 1H signals:
- Chemical Shift (ppm)
- Multiplicity
- 1.52
- br d
- 1.57-1.67
- m
- 1.81
- br d
- 1.88
- m
- 2.87
- dd
- 2.90
- m
- 3.12
- dd
- 3.15
- m
- 3.65
- m
- 3.83
- m
- 3.94
- br d
- 4.40
- br s
- 4.46
- m
- 4.50
- dd
- 4.70
- m
- 5.06
- d
- 6.46
- br
- 6.94
- s
- 7.29
- s
- 7.99
- d
- 8.17
- d
- 8.30
- m
- 8.57
- br d
- 8.95
- d
- 9.06
- br d
- 14.09
- br
- 14.27
- br
- —
- —
- D) 13C-NMR spectrum recorded at 150 Mhz, at 25° C. in DMSO-d6 and trifluoroacetic acid (drops) showing the following 13C signals
- Chemical Shift
- (ppm)
- Multiplicity
- 15.9
- t
- 27.19
- t
- 28.14
- t
- 35.31
- t
- 42.86
- t
- 50.13
- d
- 51.30
- d
- 56.86
- d
- 59.71
- d
- 64.07
- d
- 65.11
- d
- 66.88
- d
- 67.76
- t
- 116.83
- d
- 118.49
- d
- 128.41
- s
- 129.03
- s
- 133.65
- d
- 139.66
- s
- 156.73
- s
- 167.39
- s
- 170.16
- s
- 171.29
- s
- 171.65
- s
- E) Retention time 14.1 min, determined by using an analytical HPLC pump Shimadzu® LC10-AS, equipped with a chromatographic column Altima® RP18, 5 μm, 250×4.6 mm i.d column;
- isocratic elution performed at 1 ml/min flow rate, with 40 mM ammonium formate buffer, brought to pH 4.5 by addition of formic acid;
- UV detection at 230 nm;
- F) possesses acid functions and basic functions;
- and
- G) inhibits the growth of Moraxella catarrhalis;
- inhibits the growth of Eseherichia coli and Bacillus subtilis when these bacteria are cultivated in minimal media;
- shows marginal activity against Streptococcus pneumoniae;
- does not inhibit growth of Candida albicans, or
- mixtures thereof;
- and
- pharmaceutically acceptable salts thereof.
145 more elements
Dependencies are inferred from the claim text.