| Identification | Back Directory | [Name]
Novobiocin | [CAS]
303-81-1 | [Synonyms]
pa93
novo-r
C05080
U 6391
albamix
cathocin
inamycin
robiocina
sirbiocina
cathomycin
cardelmycin
spheromycin
stilbiocina
antibioticpa-93
crystallinicacid
Novobiocin (200 mg)
3-(3-methyl-2-butenyl)-
NOVOBIOCIN, USP STANDARD
NOVOBIOCIN (200 MG)H0D3271012UG/MG(DR)
AlbaMycin, VulcaMycin, PA 93, WS 6629, Griseoflavin, S 800.
-hexopyranosyl)oxy)-4-hydroxy-8-methyl-2-oxo-2h-1-benzopyran-3-yl)-4-hydroxy-
benzamide,n-(7-((3-o-(aminocarbonyl)-6-deoxy-5-c-methyl-4-o-methyl-beta-l-lyxo
7-[4'-(Carbamoyloxy)-tetrahydro-3'-hydroxy-5'-methoxy-6',6'-dimethylpyran-2'-yloxy]-4-hydroxy-3-[4''-hydroxy (3''-methyl-2''-butenyl)-benzamide]-8-methylcoumarin | [EINECS(EC#)]
206-146-3 | [Molecular Formula]
C31H36N2O11 | [MOL File]
303-81-1.mol | [Molecular Weight]
612.628 |
| Chemical Properties | Back Directory | [Appearance]
A light-yellow to white antibiotic produced by Streptomyces niveus. Available as calcium
and sodium salts. | [Melting point ]
170-172 °C | [alpha ]
D24 -63.0° (c = 1 in ethanol) | [Boiling point ]
657.29°C (rough estimate) | [density ]
1.3448 | [refractive index ]
1.5800 (estimate) | [storage temp. ]
Hygroscopic, -20°C Freezer, Under inert atmosphere | [solubility ]
DMSO (Slightly), Methanol (Slightly) | [form ]
Solid | [pka]
pKa1 4.3; pKa2 9.1(at 25℃) | [color ]
White to Pale Yellow |
| Hazard Information | Back Directory | [Uses]
Novobiocin is an aminocoumarin antibiotic isolated from a number of species of Streptomyces. Novobiocin exhibits broad spectrum Gram positive activity and was used clinically. Novobiocin is a potent inhibitor of bacterial DNA gyrase and a competitive inhibitor of the ATPase reaction catalysed by GyrB. | [Uses]
Novobiocin is an aminocoumarin antibiotic isolated from a number of species of Streptomyces. Novobiocin exhibits broad spectrum Gram positive antibiotic activity and was used clinically. Novobiocin is a potent inhibitor of bacterial DNA gyrase and a competitive inhibitor of the ATPase reaction catalysed by GyrB. | [Definition]
ChEBI: A coumarin-derived antibiotic obtained from Streptomyces niveus. | [Hazard]
May have damaging side effects. | [Description]
Novobiocin (Albamycin, Cathamycin, Spheromycin) is an aminocoumarin antibiotic originally isolated from Streptomyces niveus in the Upjohn Research Laboratories and initially was given the generic name of ‘streptonivicin’ . It was also isolated almost simultaneously in other laboratories, and was given several other names. Novobiocin inhibits the GyrB subunit of DNA gyrase and is primarily active against Gram-positive microorganisms. It was used under the trade name Albamycin and was withdrawn from the market in the US. Its latest use included eradication of methicillin-resistant Staphylococcus aureus (MRSA) and other resistant microorganisms. In addition, it has been applied in cancer therapy. | [Chemical Properties]
A light-yellow to white antibiotic produced by Streptomyces niveus. Available as calcium
and sodium salts. | [Originator]
Albamycin,Upjohn,US,1956 | [Manufacturing Process]
The preparation of novobiocin by fermentation is described in US Patent 3,049,534 as follows: A medium containing 2% soybean meal, 1% dextrose, 0.25% sodium chloride and 0.75% distiller's solubles was made up in tap water. About 25 ml of the prepared medium was placed in a 75 ml vial and sterilized by heating at 120°C for 20 minutes. The sterilized medium was then inoculated with a vegetative culture of Streptomyces spheroides MA-319 (NRRL 2449), and the vial loosely stoppered with cotton. The vial was then placed on a shaking machine with an amplitude of 1? inches at 28°C for 6 days. At the end of this fermentation time, the fermented broth was assayed using the cylinder-plate method with Bacillus megatherium ATCC 9885 as the assay organism and found to have an activity of 600 units/ml or 30 mcg/ml of novobiocin. The production of larger quantities of novobiocin by submerged fermentation in suitable tanks is also described in US Patent 3,049,534.
The preparation of novobiocin by a synthetic route is described in US Patent 2,966,484, as well as in US Patent 2,925,411.
| [Brand name]
Albamycin. | [Therapeutic Function]
Antibiotic | [World Health Organization (WHO)]
Novobiocin, an antibiotic with a narrow spectrum of activity, was
introduced in 1956. Its use was subsequently associated with serious adverse
effects including blood dyscrasias. In view of its toxicity there are no current valid
indications for its use. Although preparations containing novobiocin may remain
available in some countries it has largely lapsed into disuse. | [Antimicrobial activity]
Novobiocin is active against some of these bacteria, such as S. aureus (including beta-lactamase-producing strains) and the pneumococcus. Its MIC against strains of MRSA is r 0.25 mg/L, and against such strains when combined with rifampicin it shows neither synergy nor antagonism, but emergence of resistance to either agent seems to be prevented. Streptococcus pyogenes is much less susceptible and Streptococcus viridans strains vary in their sensitivity. Enterococcus faecalis is usually moderately resistant, but E. faecium, including multiresistant strains, is susceptible. Gram-positive bacilli, such as Bacillus anthracis, Clostridium tetani, C. perfringens, and Corynebacterium diphtheriae, are novobiocin susceptible. S. saprophyticus is intrinsically resistant due to alteration in the GyrB gene. | [Mechanism of action]
Novobiocin inhibits DNA and bacterial protein synthesis by binding to the GyrB subunit of DNA topoisomerase II (gyrase), an enzyme which is associated with the supercoiling of DNA. Although quinolones also target DNA gyrase, the binding site for quinolones is different. Like other aminocoumarin antibiotics, novobiocin acts as a competitive inhibitor of the ATPase reaction catalyzed by GyrB. There is also activity against topoisomerase IV . | [Pharmacokinetics]
Novobiocin is well absorbed from the alimentary tract. After a single oral dose of 0.5 g to adults, a peak serum level of 10–20 mg/l levels may persist for 24 h or longer. Doubling the dose doubles the serum concentrations. If a dose of 0.5 g is administered orally every 6 h, there is often some accumulation, and after four doses the peak serum level may reach 100 mg/l. When an oral dose of 0.5 g novobiocin was given orally twice daily to adult volunteers for 27 doses, the mean serum concentration prior to dose 27 was 21.6 mg/l; this rose to a mean peak serum level 2 h after the dose of 55.5 mg/l. When oral rifampicin (300 mg 12-hourly) was given concomitantly, the comparative values before and after the last dose were 6.9 and 49.2 mg/l, respectively. Similarly, novobiocin levels were lower when rifampicin was co-administered than when novobiocin was given alone at 8 h (7.9 versus 21.6 mg/l) and at 12 h after the 27th dose (3.0 versus 16.0 mg/l). The half-life of novobiocin (5.85 h) was reduced to 2.66 h when administered in combination with rifampicin. | [Clinical Use]
Novobiocin formerly had a role in the treatment of staphylococcal infections. With the advent of the penicillinase-resistant penicillins and other anti-staphylococcal agents, novobiocin is no longer used for this indication, except perhaps as an adjunct to other drugs for the treatment of methicillin-resistant staphylococcal infections. For instance, novobiocin/sodium fusidate and novobiocin/rifampicin combinations have been used successfully to treat staphylococcal infections of this nature. | [Veterinary Drugs and Treatments]
Novobiocin is approved as a single agent and in combination with
penicillin G for use in dry dairy cattle as a mastitis tube. Novobiocin
is available in combination with tetracycline and prednisolone for
oral use in dogs. |
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