Novobiocin

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Novobiocin
Clinical data
Pregnancy; category	?;
Routes of; administration	intravenous
ATC code	? {{}};
Legal status
Legal status	?;
Pharmacokinetic data
Bioavailability	negligible oral bioavailability
Metabolism	excreted unchanged
Elimination half-life	6 hours
Excretion	renal
Identifiers
	IUPAC name 4-Hydroxy-3-[4-hydroxy-3-(3-methylbut-2-enyl)benzamido]-8-methylcoumarin-7-yl 3-O-carbamoyl-5,5-di-C-methyl-α-l-lyxofuranoside;
CAS Number	303-81-1;
PubChem CID	7526;
DrugBank	APRD00694;
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
Formula	C31H36N2O11
Molar mass	612.624

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Novobiocin is an aminocoumarin antibiotic that was produced by the actinomycete Streptomyces niveus, which has recently been identified as a subjective synonym for S. spheroides^[1] a member of the order Actinobacteria . Other aminocoumarin antibiotics include clorobiocin and coumermycin A1.^[2] Novobiocin was first reported in the middle of 1950s (called then streptonivicin).^[3]^[4]

Mechanism of action

The molecular basis of action of novobiocin, and other related drugs clorobiocin and coumermycin A1 has been examined.^[2]^[5]^[6]^[7]^[8] Aminocoumarins are very potent inhibitors of bacterial DNA gyrase and work by targeting the GyrB subunit of the enzyme involved in energy tranduction. Novobiocin as well as the other aminocoumarin antibiotics act as competitive inhibitors of the ATPase reaction catalysed by GyrB. The potency of novobiocin is considerably higher than that of the fluoroquinolones that also target DNA gyrase, but at a different site on the enzyme. The GyrA subunit is involved in the DNA nicking and ligation activity.

Structure

Novobiocin is an aromatic ether compound. Novobiocin may be divided up into three entities; a benzoic acid derivative, a coumarin residue, and the sugar novobiose.^[5]. X-ray crytallographic studies have found that the drug-receptor complex of Novobiocin and DNA Gyrase shows that ATP and Novobiocin have overlapping binding sites on the gyrase molecule.^[9] The overlap of the coumarin and ATP-binding sites is consistent with aminocoumarins being competitive inhibitors of the ATPase activity.^[10]

Structure Activity Relationship

In structure activity relationship experiments it was found that removal of the carbamoyl group located on the novobiose sugar lead to a dramatic decrease in inhibitory activity of novobiocin. ^[10]

Clinical Use

Novobiocin was licenced for clinical use under the tradename Albamycin® (Pharmacia And Upjohn) in the 1960s. Its efficacy has been demonstrated in preclinical and clinical trials.^[11]^[12] It has since been withdrawn from the market.^[13] Novobiocin is effective antistaphylococcal agent used in the treatment of MRSA^[14]. It is also active against Staphylococcus epidermidis and may be used to differentiate from the other coagulase-negative Staphylococcus saprophyticus, which is resistant to novobiocin, in culture.

References

↑ Lanoot, B., M. Vancanneyt, I. Cleenwerck, L. Wang, W. Li, Z. Liu, and J. Swings. 2002. The search for synonyms among streptomycetes by with SDS-PAGE of whole-cell proteins. Emendation of the species Streptomyces aurantiacus, Streptomyces cacaoi subsp. cacaoi, Streptomyces caeruleus and Streptomyces violaceus. Int. J. Syst. Evol. Microbiol. 52:823-829.
↑ ^2.0 ^2.1 Alessandra da Silva Eustáquio (2004) Biosynthesis of aminocoumarin antibiotics in Streptomyces: Generation of structural analogues by genetic engineering and insights into the regulation of antibiotic production. DISSERTATION
↑ Hoeksema, H., Johnson, J. L., and Hinman, J. W. (1955). Structural studies on streptonivicin, a new antibiotic. J Am Chem Soc, 77, 6710-6711.
↑ Smith, C. G., Dietz, A., Sokolski, W. T., and Savage, G. M. (1956). Streptonivicin, a new antibiotic. I. Discovery and biologic studies. Anitbiotics & Chemotherapy, 6, 135- 142.
↑ ^5.0 ^5.1 Maxwell, A. (1993). The interaction between coumarin drugs and DNA gyrase. Mol Microbiol, 9, 681-686.
↑ Maxwell, A. (1999). DNA gyrase as a drug target. Biochem Soc Trans, 27, 48-53.
↑ Lewis, R. J., Tsai, F. T. F., and Wigley, D. B. (1996). Molecular mechanisms of drug inhibition of DNA gyrase. Bioessays, 18, 661-671.
↑ Maxwell, A., and Lawson, D. M. (2003). The ATP-binding site of type II topoisomerases as a target for antibacterial drugs. Curr Top Med Chem, 3, 283-303.
↑ F.T.F. Tsai, O.M. Singh, T.Skarzynski, A.J. Wonacott, S. Weston, A. Tucker, R.A. Pauptit, A.L. Breeze, J.P. Poyser, R. O'Brien et al., The high-resolution crystal structure of a 24-kDa gyrase B fragment from E. coli complexed with one of the most potent coumarin inhibitors, clorobiocin. Proteins 28 (1997), pp. 41–52
↑ ^10.0 ^10.1 R.H. Flatman, A. Eustaquio, S. Li, L. Heide, and A. Maxwell (2006) Structure-Activity Relationships of Aminocoumarin-Type Gyrase and Topoisomerase IV Inhibitors Obtained by Combinatorial Biosynthesis Antimicrob Agents Chemother. 50(4): 1136–1142.
↑ Raad, I., Darouiche, R., Hachem, R., Sacilowski, M., and Bodey, G. P. (1995). Antibiotics and prevention of microbial colonization of catheters. Antimicrob Agents Chemother, 39, 2397-2400.
↑ Raad, I. I., Hachem, R. Y., Abi-Said, D., Rolston, K. V. I., Whimbey, E., Buzaid, A.C., and Legha, S. (1998). A prospective crossover randomized trial of novobiocinand rifampin prophylaxis for the prevention of intravascular catheter infections in cancer patients treated with interleukin-2. Cancer, 82, 403-411.
↑ http://fda-drugs.legalview.com/legal-issue/albamycin/
↑ T.J. Walsh et al.(1993) Randomized Double-Blinded Trial of Rifampin with Either Novobiocin or Trimethoprim-Sulfamethoxazole against Methicillin-Resistant Staphylococcus aureus Colonization: Prevention of Antimicrobial Resistance and Effect of Host Factors on Outcome. Antimicrobial agents and chemotherapy Vol 37 No 6 p. 1334-1342

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[1] Lanoot, B., M. Vancanneyt, I. Cleenwerck, L. Wang, W. Li, Z. Liu, and J. Swings. 2002. The search for synonyms among streptomycetes by with SDS-PAGE of whole-cell proteins. Emendation of the species Streptomyces aurantiacus, Streptomyces cacaoi subsp. cacaoi, Streptomyces caeruleus and Streptomyces violaceus. Int. J. Syst. Evol. Microbiol. 52:823-829.

[E-2] 2.0 ^2.1 Alessandra da Silva Eustáquio (2004) Biosynthesis of aminocoumarin antibiotics in Streptomyces: Generation of structural analogues by genetic engineering and insights into the regulation of antibiotic production. DISSERTATION

[3] Hoeksema, H., Johnson, J. L., and Hinman, J. W. (1955). Structural studies on streptonivicin, a new antibiotic. J Am Chem Soc, 77, 6710-6711.

[4] Smith, C. G., Dietz, A., Sokolski, W. T., and Savage, G. M. (1956). Streptonivicin, a new antibiotic. I. Discovery and biologic studies. Anitbiotics & Chemotherapy, 6, 135- 142.

[M-5] 5.0 ^5.1 Maxwell, A. (1993). The interaction between coumarin drugs and DNA gyrase. Mol Microbiol, 9, 681-686.

[6] Maxwell, A. (1999). DNA gyrase as a drug target. Biochem Soc Trans, 27, 48-53.

[7] Lewis, R. J., Tsai, F. T. F., and Wigley, D. B. (1996). Molecular mechanisms of drug inhibition of DNA gyrase. Bioessays, 18, 661-671.

[8] Maxwell, A., and Lawson, D. M. (2003). The ATP-binding site of type II topoisomerases as a target for antibacterial drugs. Curr Top Med Chem, 3, 283-303.

[9] F.T.F. Tsai, O.M. Singh, T.Skarzynski, A.J. Wonacott, S. Weston, A. Tucker, R.A. Pauptit, A.L. Breeze, J.P. Poyser, R. O'Brien et al., The high-resolution crystal structure of a 24-kDa gyrase B fragment from E. coli complexed with one of the most potent coumarin inhibitors, clorobiocin. Proteins 28 (1997), pp. 41–52

[Flatman2006-10] 10.0 ^10.1 R.H. Flatman, A. Eustaquio, S. Li, L. Heide, and A. Maxwell (2006) Structure-Activity Relationships of Aminocoumarin-Type Gyrase and Topoisomerase IV Inhibitors Obtained by Combinatorial Biosynthesis Antimicrob Agents Chemother. 50(4): 1136–1142.

[11] Raad, I., Darouiche, R., Hachem, R., Sacilowski, M., and Bodey, G. P. (1995). Antibiotics and prevention of microbial colonization of catheters. Antimicrob Agents Chemother, 39, 2397-2400.

[12] Raad, I. I., Hachem, R. Y., Abi-Said, D., Rolston, K. V. I., Whimbey, E., Buzaid, A.C., and Legha, S. (1998). A prospective crossover randomized trial of novobiocinand rifampin prophylaxis for the prevention of intravascular catheter infections in cancer patients treated with interleukin-2. Cancer, 82, 403-411.

[13] ttp://fda-drugs.legalview.com/legal-issue/albamycin/

[14] T.J. Walsh et al.(1993) Randomized Double-Blinded Trial of Rifampin with Either Novobiocin or Trimethoprim-Sulfamethoxazole against Methicillin-Resistant Staphylococcus aureus Colonization: Prevention of Antimicrobial Resistance and Effect of Host Factors on Outcome. Antimicrobial agents and chemotherapy Vol 37 No 6 p. 1334-1342

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