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Novobiocin

July 24, 2017
Common Name

Novobiocin Description

Novobiocin is only found in individuals that have used or taken this drug. It 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) [PubChem]Novobiocin is an aminocoumarin. Aminocoumarins are very potent inhibitors of bacterial DNA gyrase and work by inhibiting 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. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source N-{7-[(3-O-carbamoyl-6-deoxy-5-methyl-4-O-methyl-beta-D-gliopyranosyl)oxy]-4-hydroxy-8-methyl-2-oxo-2H-chromen-3-yl}-4-hydroxy-3-(3-methylbut-2-en-1-yl)benzamideChEBI NovobiocinaChEBI NovobiocineChEBI NovobiocinumChEBI N-{7-[(3-O-carbamoyl-6-deoxy-5-methyl-4-O-methyl-b-D-gliopyranosyl)oxy]-4-hydroxy-8-methyl-2-oxo-2H-chromen-3-yl}-4-hydroxy-3-(3-methylbut-2-en-1-yl)benzamideGenerator N-{7-[(3-O-carbamoyl-6-deoxy-5-methyl-4-O-methyl-β-D-gliopyranosyl)oxy]-4-hydroxy-8-methyl-2-oxo-2H-chromen-3-yl}-4-hydroxy-3-(3-methylbut-2-en-1-yl)benzamideGenerator Antibiotic pa-93HMDB Crystallinic acidHMDB NOVHMDB Sodium, novobiocinMeSH StreptonivicinMeSH Calcium, novobiocinMeSH Monosodium salt novobiocinMeSH Novobiocin, monosodium saltMeSH Novobiocin calciumMeSH Novobiocin sodiumMeSH

Chemical Formlia

C31H36N2O11 Average Molecliar Weight

612.6243 Monoisotopic Molecliar Weight

612.231910004 IUPAC Name

(3R,4S,5R,6R)-5-hydroxy-6-({4-hydroxy-3-[4-hydroxy-3-(3-methylbut-2-en-1-yl)benzamido]-8-methyl-2-oxo-2H-chromen-7-yl}oxy)-3-methoxy-2,2-dimethyloxan-4-yl carbamate Traditional Name

novobiocin CAS Registry Number

303-81-1 SMILES

CO[C@@H]1[C@@H](OC(N)=O)[C@@H](O)[C@H](OC2=C(C)C3=C(C=C2)C(O)=C(NC(=O)C2=CC=C(O)C(CC=C(C)C)=C2)C(=O)O3)OC1(C)C

InChI Identifier

InChI=1S/C31H36N2O11/c1-14(2)7-8-16-13-17(9-11-19(16)34)27(37)33-21-22(35)18-10-12-20(15(3)24(18)42-28(21)38)41-29-23(36)25(43-30(32)39)26(40-6)31(4,5)44-29/h7,9-13,23,25-26,29,34-36H,8H2,1-6H3,(H2,32,39)(H,33,37)/t23-,25+,26-,29-/m1/s1

InChI Key

YJQPYGGHQPGBLI-KGSXXDOSSA-N Chemical Taxonomy Description

This compound belongs to the class of organic compounds known as coumarin glycosides. These are aromatic compounds containing a carbohydrate moiety glycosidically bound to a coumarin moiety. Kingdom

Organic compounds Super Class

Phenylpropanoids and polyketides Class

Coumarins and derivatives Sub Class

Coumarin glycosides Direct Parent

Coumarin glycosides Alternative Parents

  • Phenolic glycosides
  • 4-hydroxycoumarins
  • Hexoses
  • O-glycosyl compounds
  • 1-benzopyrans
  • Benzamides
  • Benzoyl derivatives
  • 1-hydroxy-2-unsubstituted benzenoids
  • Pyranones and derivatives
  • Oxanes
  • Vinylogous acids
  • Carbamate esters
  • Heteroaromatic compounds
  • Secondary carboxylic acid amides
  • Secondary alcohols
  • Organic carbonic acids and derivatives
  • Lactones
  • Dialkyl ethers
  • Oxacyclic compounds
  • Acetals
  • Carbonyl compounds
  • Organic oxides
  • Organonitrogen compounds
  • Organopnictogen compounds
  • Hydrocarbon derivatives

    • Substituents

  • Coumarin-7-o-glycoside
  • Coumarin o-glycoside
  • Phenolic glycoside
  • 4-hydroxycoumarin
  • Hydroxycoumarin
  • Hexose monosaccharide
  • O-glycosyl compound
  • Glycosyl compound
  • Benzopyran
  • 1-benzopyran
  • Benzamide
  • Benzoic acid or derivatives
  • Benzoyl
  • 1-hydroxy-2-unsubstituted benzenoid
  • Phenol
  • Pyranone
  • Pyran
  • Monocyclic benzene moiety
  • Monosaccharide
  • Oxane
  • Benzenoid
  • Heteroaromatic compound
  • Vinylogous acid
  • Carbamic acid ester
  • Carboxamide group
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Lactone
  • Carbonic acid derivative
  • Ether
  • Dialkyl ether
  • Acetal
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Oxacycle
  • Organic nitrogen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

  • monocarboxylic acid amide (CHEBI:28368 )
  • monosaccharide derivative (CHEBI:28368 )
  • hexoside (CHEBI:28368 )
  • hydroxycoumarin (CHEBI:28368 )
  • Aromatic compounds (C05080 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Nucleic Acid Synthesis Inhibitors

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Cytoplasm
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility9.66e-03 g/LNot Available LogP4.1Not Available

    Predicted Properties

    Property Value Source Water Solubility0.0097 mg/mLALOGPS logP3.07ALOGPS logP3.26ChemAxon logS-4.8ALOGPS pKa (Strongest Acidic)6.96ChemAxon pKa (Strongest Basic)-3.9ChemAxon Physiological Charge-1ChemAxon Hydrogen Acceptor Count9ChemAxon Hydrogen Donor Count5ChemAxon Polar Surface Area196.1 Å2ChemAxon Rotatable Bond Count9ChemAxon Refractivity158.24 m3·mol-1ChemAxon Polarizability63.97 Å3ChemAxon Number of Rings4ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , negativesplash10-03di-0000009000-b1cde524a6fa9a8469fbView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , negativesplash10-03di-0000449000-4b6598caa7dcff199d3cView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , negativesplash10-0230-0005904000-5fe18777e8a9abd4250aView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , negativesplash10-0a59-0096200000-4ea433cdc759c03b554dView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , negativesplash10-0a4i-0091000000-912d33bd49e7c2686b5bView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , positivesplash10-03di-0141009000-46efbf9ab2bd123e3329View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , positivesplash10-000i-0900000000-e321cd21925818d2156aView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , positivesplash10-000i-0900000000-6425ec6e8bbb44075cf4View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , positivesplash10-000i-0900000000-32fb8ff4ec7fde30b513View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , positivesplash10-000i-0900000000-004f89ab3d920e8c5936View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , positivesplash10-000j-0933000000-cd71bb412108d603ba2dView in MoNA Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Cytoplasm
  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01051

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01051

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01051 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    10226117 KEGG Compound ID

    C05080 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Novobiocin NuGOwiki Link

    HMDB15185 Metagene Link

    HMDB15185 METLIN ID

    Not Available PubChem Compound

    54675769 PDB ID

    NOV ChEBI ID

    148697

    Product: LY-411575 (isomer 4)

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. DAVID NA, BURGNER PR: Clinical effectiveness and safety of novobiocin. Antibiotic Med Clin Ther (New York). 1956 Apr;2(4):219-29. [PubMed:13303117 ]
    2. CORBIN EE, PRIGOT A: Novobiocin; absorption, diffusion, and excretion studies. Antibiot Annu. 1956-1957:392-5. [PubMed:13425410 ]
    3. Singh G, Jayanarayan KG, Dey CS: Novobiocin induces apoptosis-like cell death in topoisomerase II over-expressing arsenite resistant Leishmania donovani. Mol Biochem Parasitol. 2005 May;141(1):57-69. [PubMed:15811527 ]
    4. Burlison JA, Neckers L, Smith AB, Maxwell A, Blagg BS: Novobiocin: redesigning a DNA gyrase inhibitor for selective inhibition of hsp90. J Am Chem Soc. 2006 Dec 6;128(48):15529-36. [PubMed:17132020 ]
    5. Vickers AA, Chopra I, ONeill AJ: Intrinsic novobiocin resistance in Staphylococcus saprophyticus. Antimicrob Agents Chemother. 2007 Dec;51(12):4484-5. Epub 2007 Sep 17. [PubMed:17876001 ]

    Transporters

    General function:
    Involved in ATP binding
    Specific function:
    Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes
    Gene Name:
    ABCB11
    Uniprot ID:
    O95342
    Molecular weight:
    146405.8
    References
    1. Saito H, Osumi M, Hirano H, Shin W, Nakamura R, Ishikawa T: Technical pitfalls and improvements for high-speed screening and QSAR analysis to predict inhibitors of the human bile salt export pump (ABCB11/BSEP). AAPS J. 2009 Sep;11(3):581-9. doi: 10.1208/s12248-009-9137-9. Epub 2009 Aug 18. [PubMed:19688600 ]
    General function:
    Involved in ATP binding
    Specific function:
    Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123
    Gene Name:
    ABCG2
    Uniprot ID:
    Q9UNQ0
    Molecular weight:
    72313.5
    References
    1. Gedeon C, Behravan J, Koren G, Piquette-Miller M: Transport of glyburide by placental ABC transporters: implications in fetal drug exposure. Placenta. 2006 Nov-Dec;27(11-12):1096-102. Epub 2006 Feb 3. [PubMed:16460798 ]
    2. Shiozawa K, Oka M, Soda H, Yoshikawa M, Ikegami Y, Tsurutani J, Nakatomi K, Nakamura Y, Doi S, Kitazaki T, Mizuta Y, Murase K, Yoshida H, Ross DD, Kohno S: Reversal of breast cancer resistance protein (BCRP/ABCG2)-mediated drug resistance by novobiocin, a coumermycin antibiotic. Int J Cancer. 2004 Jan 1;108(1):146-51. [PubMed:14618629 ]
    3. Elahian F, Kalalinia F, Behravan J: Evaluation of indomethacin and dexamethasone effects on BCRP-mediated drug resistance in MCF-7 parental and resistant cell lines. Drug Chem Toxicol. 2010 Apr;33(2):113-9. doi: 10.3109/01480540903390000. [PubMed:20307139 ]
    General function:
    Involved in transporter activity
    Specific function:
    Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds
    Gene Name:
    SLC22A11
    Uniprot ID:
    Q9NSA0
    Molecular weight:
    59970.9
    References
    1. Duan P, You G: Novobiocin is a potent inhibitor for human organic anion transporters. Drug Metab Dispos. 2009 Jun;37(6):1203-10. doi: 10.1124/dmd.109.026880. Epub 2009 Mar 12. [PubMed:19282394 ]
    General function:
    Involved in ion transmembrane transporter activity
    Specific function:
    Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS). Mediates the sodium-independent uptake of p- aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3-azido- 3-deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro- phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2- furanpropionate (CMPF), cidofovir, adefovir, 9-(2- phosphonylmethoxyethyl) guanine (PMEG), 9-(2- phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p- chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid. PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate
    Gene Name:
    SLC22A6
    Uniprot ID:
    Q4U2R8
    Molecular weight:
    61815.8
    References
    1. Duan P, You G: Novobiocin is a potent inhibitor for human organic anion transporters. Drug Metab Dispos. 2009 Jun;37(6):1203-10. doi: 10.1124/dmd.109.026880. Epub 2009 Mar 12. [PubMed:19282394 ]

    PMID: 17659592

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