Tmic
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Record Information
Version2.0
Creation Date2009-07-03 22:03:17 UTC
Update Date2014-12-24 20:25:34 UTC
Accession NumberT3D2478
Identification
Common NameLevofloxacin
ClassSmall Molecule
DescriptionLevofloxacin is a synthetic fluoroquinolone antibacterial agent that inhibits the supercoiling activity of bacterial DNA gyrase, halting DNA replication. Levofloxacin is marketed by Ortho-McNeil under the trade name Levaquin. Chemically, levofloxacin is the S-enantiomer (L-isomer) of ofloxacin.
Compound Type
  • Amide
  • Amine
  • Anti-Bacterial Agent
  • Anti-Infective Agent, Urinary
  • Drug
  • Ester
  • Ether
  • Food Toxin
  • Metabolite
  • Nucleic Acid Synthesis Inhibitor
  • Organic Compound
  • Organofluoride
  • Quinolone
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(-)-Ofloxacin
(3S)-(-)-9-Fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid
(S)-(-)-9-Fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzooxazine-6-carboxylic acid
(S)-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido(1,2,3-de)-1,4-benzoxazine-6-carboxylic acid
(S)-Ofloxacin
Cravit
Elequine
Floxel
Floxin
Iquix
L-ofloxacin
Leroxacin
Levaquin
Levofloxacin hydrate
Levofloxacine
Levofloxacino
Levofloxacinum
Levokacin
Levox
Levoxacin
Mosardal
Nofaxin
Ofloxacin
Ofloxacin S-(-)-form
Quixin
Reskuin
Tavanic
Chemical FormulaC18H20FN3O4
Average Molecular Mass361.368 g/mol
Monoisotopic Mass361.144 g/mol
CAS Registry Number100986-85-4
IUPAC Name(2S)-7-fluoro-2-methyl-6-(4-methylpiperazin-1-yl)-10-oxo-4-oxa-1-azatricyclo[7.3.1.0⁵,¹³]trideca-5(13),6,8,11-tetraene-11-carboxylic acid
Traditional Namelevofloxacin
SMILES[H][C@]1(C)COC2=C3N1C=C(C(O)=O)C(=O)C3=CC(F)=C2N1CCN(C)CC1
InChI IdentifierInChI=1S/C18H20FN3O4/c1-10-9-26-17-14-11(16(23)12(18(24)25)8-22(10)14)7-13(19)15(17)21-5-3-20(2)4-6-21/h7-8,10H,3-6,9H2,1-2H3,(H,24,25)/t10-/m0/s1
InChI KeyInChIKey=GSDSWSVVBLHKDQ-JTQLQIEISA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as quinoline carboxylic acids. These are quinolines in which the quinoline ring system is substituted by a carboxyl group at one or more positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassQuinoline carboxylic acids
Direct ParentQuinoline carboxylic acids
Alternative Parents
Substituents
  • Quinoline-3-carboxylic acid
  • Fluoroquinolone
  • N-arylpiperazine
  • Aminoquinoline
  • Haloquinoline
  • Dihydroquinolone
  • Benzoxazine
  • Dihydroquinoline
  • Pyridine carboxylic acid
  • Pyridine carboxylic acid or derivatives
  • Tertiary aliphatic/aromatic amine
  • Dialkylarylamine
  • N-alkylpiperazine
  • N-methylpiperazine
  • Alkyl aryl ether
  • Benzenoid
  • Pyridine
  • Aryl fluoride
  • Piperazine
  • Aryl halide
  • 1,4-diazinane
  • Vinylogous amide
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Amino acid or derivatives
  • Amino acid
  • Azacycle
  • Oxacycle
  • Carboxylic acid derivative
  • Carboxylic acid
  • Ether
  • Monocarboxylic acid or derivatives
  • Organonitrogen compound
  • Organic nitrogen compound
  • Amine
  • Organic oxygen compound
  • Organooxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Organofluoride
  • Hydrocarbon derivative
  • Organohalogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Prostate
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceClear yellow to clear greenish-yellow liquid (7).
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityInsoluble
LogP2.1
Predicted Properties
PropertyValueSource
Water Solubility1.44 g/LALOGPS
logP-0.02ALOGPS
logP0.65ChemAxon
logS-2.4ALOGPS
pKa (Strongest Acidic)5.45ChemAxon
pKa (Strongest Basic)6.2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area73.32 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity94.94 m³·mol⁻¹ChemAxon
Polarizability36.69 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-2019000000-30d77332fe9feb70a82dView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-01dl-7009600000-d322709717558bd09e25View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, N/A (Annotated)splash10-00gm-1315975420-b0c4e6cdef799fda69b4View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, N/A (Annotated)splash10-0abc-3459425420-e8a4ecd2f8aea93fa660View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, N/A (Annotated)splash10-0h9p-3513893500-1d5c8069419fa2c37ebbView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-03di-0009000000-63138044688fa3ab0792View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-02t9-0019000000-265eec70cbb77077fbfaView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-03di-1290000000-3ff2c315dfac97ded8c5View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0axr-1980000000-e31472e2487627c51ceaView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0adl-1930000000-3cd445f16118ecf3f610View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-03di-0049000000-3cbab894a4b0d1165e7dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-03di-2492000000-62b30ac9148b06791816View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0009000000-6e3992e2c7f71e2e2d60View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-02tc-0009000000-8e0f1b0fc3b80969c0ddView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0pi3-7097000000-363d82fc0e563a2423b0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-02t9-0009000000-bf579599f29511ea990cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0670-0096000000-9d4af124e757cd0455bbView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014r-0091000000-c5e349004a62406fb095View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureIngestion; injection; skin contact (7). Absorption of ofloxacin after single or multiple doses of 200 to 400 mg is predictable, and the amount of drug absorbed increases proportionately with the dose.
Mechanism of ToxicityLevofloxacin inhibits bacterial type II topoisomerases, topoisomerase IV and DNA gyrase. Levofloxacin, like other fluoroquinolones, inhibits the A subunits of DNA gyrase, two subunits encoded by the gyrA gene. This results in strand breakage on a bacterial chromosome, supercoiling, and resealing; DNA replication and transcription is inhibited.
MetabolismMainly excreted as unchanged drug (87%); undergoes limited metabolism in humans. Levofloxacin is rapidly and essentially completely absorbed after oral administration. It is distributed into body tissues, especially in the skin and lung tissues. Levofloxacin is stereochemically stable in plasma and urine and does not invert metabolically to its enantiomer, D-ofloxacin. Levofloxacin undergoes limited metabolism in humans and is primarily excreted as unchanged drug in the urine. Following oral administration, approximately 87% of an administered dose was recovered as unchanged drug in urine within 48 hours, whereas less than 4% of the dose was recovered in feces in 72 hours. Less than 5% of an administered dose was recovered in the urine as the desmethyl and N-oxide metabolites, the only metabolites identified in humans. These metabolites have little relevant pharmacological activity. Levofloxacin is excreted largely as unchanged drug in the urine (6). Route of Elimination: Mainly excreted as unchanged drug in the urine. Half Life: 6-8 hours
Toxicity ValuesLD50: 640 mg/kg (Oral, Rat)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms: Corynebacterium species, Staphylococus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus (Groups C/F/G), Viridans group streptococci, Acinetobacter lwoffii, Haemophilus influenzae, Serratia marcescens. Levofloxacin is a synthetic chemotherapeutic agent used to treat severe and life threatening bacterial infection (6).
Minimum Risk LevelNot Available
Health EffectsIrreversible peripheral neuropathy, central nervous system toxicity, cardiovascular toxicity, tendon / articular toxicity, and hepatic toxicity. Toxic epidermal necrolysis, coagulation abnormalities and pancytopenia are other possible adverse effect of levofloxacin. Administration of commercial levofloxin (Levaquin), increased risk of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon (6, 7).
SymptomsSide effects include disorientation, dizziness, drowsiness, hot and cold flashes, nausea, slurring of speech, swelling and numbness in the face.
TreatmentIn the event of an acute overdosage, the stomach should be emptied. The patient should be observed and appropriate hydration maintained. Levofloxacin is not efficiently removed by hemodialysis or peritoneal dialysis. (6)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01137
HMDB IDHMDB01929
PubChem Compound ID149096
ChEMBL IDCHEMBL33
ChemSpider ID131410
KEGG IDC07660
UniProt IDNot Available
OMIM ID
ChEBI ID63598
BioCyc IDNot Available
CTD IDNot Available
Stitch IDLevofloxacin
PDB IDLFX
ACToR IDNot Available
Wikipedia LinkLevofloxacin
References
Synthesis Reference

Valerie Niddam-Hildesheim, “Preparation of levofloxacin and forms thereof.” U.S. Patent US20030130507, issued July 10, 2003.

MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Norrby SR: Levofloxacin. Expert Opin Pharmacother. 1999 Nov;1(1):109-19. [11249554 ]
  3. Chow AT, Chen A, Lattime H, Morgan N, Wong F, Fowler C, Williams RR: Penetration of levofloxacin into skin tissue after oral administration of multiple 750 mg once-daily doses. J Clin Pharm Ther. 2002 Apr;27(2):143-50. [11975700 ]
  4. Bielecka-Grzela S, Klimowicz A: Evaluation of ofloxacin penetration into the skin after a single oral dose assessed by cutaneous microdialysis. Pol J Pharmacol. 2003 Jul-Aug;55(4):613-8. [14581720 ]
  5. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [19212411 ]
  6. Wikipedia. Levofloxacin. Last Updated 7 August 2009. [Link]
  7. RxList: The Internet Drug Index (2009). [Link]
  8. Pharmevo (2009). Spectrix. [Link]
  9. Drugs.com [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function:
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular Weight:
126653.52 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50912.01084 uMNot AvailableBindingDB 50366826
IC50912.011 uMNot AvailableBindingDB 50366826
References
  1. Tobita M, Nishikawa T, Nagashima R: A discriminant model constructed by the support vector machine method for HERG potassium channel inhibitors. Bioorg Med Chem Lett. 2005 Jun 2;15(11):2886-90. [15911273 ]
  2. Jia L, Sun H: Support vector machines classification of hERG liabilities based on atom types. Bioorg Med Chem. 2008 Jun 1;16(11):6252-60. doi: 10.1016/j.bmc.2008.04.028. Epub 2008 Apr 16. [18448342 ]
  3. Keseru GM: Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods. Bioorg Med Chem Lett. 2003 Aug 18;13(16):2773-5. [12873512 ]
General Function:
Ubiquitin binding
Specific Function:
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).
Gene Name:
TOP2A
Uniprot ID:
P11388
Molecular Weight:
174383.88 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General Function:
Monovalent cation:proton antiporter activity
Specific Function:
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, ganciclovir and also the zwitterionic cephalosporin, cephalexin and cephradin. Seems to also play a role in the uptake of oxaliplatin (a new platinum anticancer agent). Able to transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium); a widely used herbicid. Responsible for the secretion of cationic drugs across the brush border membranes.
Gene Name:
SLC47A1
Uniprot ID:
Q96FL8
Molecular Weight:
61921.585 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5017.9 uMNot AvailableBindingDB 50366826
References
  1. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]