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HomeProduct name listNovobiocin

Novobiocin

Synonym(s):Benzamide, N-[7-[[3-O-(aminocarbonyl)-6-deoxy-5-C-methyl-4-O-methyl-?-l-lyxohexopyranosyl]oxy]-4-hydroxy-8-methyl-2-oxo-2H-1-benzopyran-3-yl]-4-hydroxy-3-
(3-methyl-2-butenyl), monohydrate;Streptonivicin

Novobiocin Structural

What is Novobiocin?

Absorption

Oral bioavailability is negligible.

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 It was used under the trade name Albamycin and was withdrawn from the market in the US.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

The Uses of Novobiocin

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.

The Uses of Novobiocin

Novobiocin is an aminocoumarin antibiotic used in the treatment of Staphylococcus epidermis.

Background

Novobiocin is an antibiotic compound derived from Streptomyces niveus. It has a chemical structure similar to coumarin. Novobiocin binds to DNA gyrase and blocks adenosine triphosphatase (ATPase) activity. (From Reynolds, Martindale The Extra Pharmacopoeia, 30th ed, p189)
Novobiocin sodium, a salt form of novobiocin, was initially approved in September 1964 and was indicated for the treatment of serious infections due to susceptible strains of Staphylococcus aureus when other less toxic antibiotics cannot be used. In 2009, the FDA determined novobiocin sodium was withdrawn from sale for reasons of safety or effectiveness.

Indications

For the treatment of infections due to staphylococci and other susceptible organisms

What are the applications of Application

Novobiocin is a potent inhibitor of bacterial DNA gyrase

Definition

ChEBI: A coumarin-derived antibiotic obtained from Streptomyces niveus.

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.

Hazard

May have damaging side effects.

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 an aminocoumarin antibiotic that was produced by the actinomycete Streptomyces niveus. Novobiocin binds to DNA gyrase, and blocks adenosine triphosphatase (ATPase) activity. Other antibiotics in the aminocoumarin class include coumermycin A1 and clorobiocin.

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.

Metabolism

Not Available

Properties of Novobiocin

Melting point: 170-172 °C
Boiling point: 657.29°C (rough estimate)
alpha  D24 -63.0° (c = 1 in ethanol)
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

Safety information for Novobiocin

Signal word Warning
Pictogram(s)
ghs
Exclamation Mark
Irritant
GHS07
GHS Hazard Statements H302:Acute toxicity,oral
H317:Sensitisation, Skin
Precautionary Statement Codes P280:Wear protective gloves/protective clothing/eye protection/face protection.

Computed Descriptors for Novobiocin

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