Identification

Name
Fleroxacin
Accession Number
DB04576
Type
Small Molecule
Groups
Experimental
Description

Fleroxacin is a broad-spectrum antimicrobial fluoroquinolone. It strongly inhibits the DNA-supercoiling activity of DNA gyrase.

Structure
Thumb
Synonyms
  • Fleroxacin
  • Fleroxacine
  • Fleroxacino
  • Fleroxacinum
  • Fleroxicin
  • FLRX
  • Megalocin
  • Megalocin (TN)
  • Megalone
  • Megalone (TN)
  • Megalosin
  • Quinodis
External IDs
RO 23-6240/000 / UNII-N804LDH51K
Categories
UNII
N804LDH51K
CAS number
79660-72-3
Weight
Average: 369.344
Monoisotopic: 369.130025941
Chemical Formula
C17H18F3N3O3
InChI Key
XBJBPGROQZJDOJ-UHFFFAOYSA-N
InChI
InChI=1S/C17H18F3N3O3/c1-21-4-6-22(7-5-21)15-12(19)8-10-14(13(15)20)23(3-2-18)9-11(16(10)24)17(25)26/h8-9H,2-7H2,1H3,(H,25,26)
IUPAC Name
6,8-difluoro-1-(2-fluoroethyl)-7-(4-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
SMILES
CN1CCN(CC1)C1=C(F)C=C2C(=O)C(=CN(CCF)C2=C1F)C(O)=O

Pharmacology

Indication

Fleroxacin is a broad-spectrum antimicrobial fluoroquinolone.

Pharmacodynamics

Fleroxacin is a broad-spectrum antimicrobial fluoroquinolone. It strongly inhibits the DNA-supercoiling activity of DNA gyrase.

Mechanism of action

The inhibition of DNA gyrase and DNA topoisomerase 2 leads ultimately to cell death as these enzymes are required for bacterial DNA replication, transcription, repair, strand supercoiling repair, and recombination.

TargetActionsOrganism
ADNA topoisomerase 2-alpha
inhibitor
Human
ADNA gyrase subunit A
inhibitor
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
ADNA topoisomerase 4 subunit A
inhibitor
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Absorption

Rapidly and well absorbed from the gastrointestinal tract after oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe therapeutic efficacy of (R)-warfarin can be increased when used in combination with Fleroxacin.
(R)-warfarinThe therapeutic efficacy of (R)-warfarin can be increased when used in combination with Fleroxacin.
(R)-warfarinThe therapeutic efficacy of (R)-warfarin can be increased when used in combination with Fleroxacin.
(S)-WarfarinThe therapeutic efficacy of (S)-Warfarin can be increased when used in combination with Fleroxacin.
(S)-WarfarinThe therapeutic efficacy of (S)-Warfarin can be increased when used in combination with Fleroxacin.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be increased when used in combination with Fleroxacin.
3-isobutyl-1-methyl-7H-xanthineThe metabolism of 3-isobutyl-1-methyl-7H-xanthine can be decreased when combined with Fleroxacin.
4-hydroxycoumarinThe therapeutic efficacy of 4-hydroxycoumarin can be increased when used in combination with Fleroxacin.
4-hydroxycoumarinThe therapeutic efficacy of 4-hydroxycoumarin can be increased when used in combination with Fleroxacin.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Fleroxacin.
Food Interactions
  • Avoid excessive coffee or tea (caffeine)
  • Avoid milk, calcium containing dairy products, iron, magnesium, zinc, antacids, or aluminum salts 2 hours before or 6 hours after using antacids while on this medication.
  • Take with a full glass of water
  • Take without regard to meals

References

Synthesis Reference
US4398029
General References
Not Available
External Links
KEGG Drug
D01716
KEGG Compound
C13179
PubChem Compound
3357
PubChem Substance
46506357
ChemSpider
3240
ChEBI
31810
ChEMBL
CHEMBL6273
Therapeutic Targets Database
DAP000928
PharmGKB
PA164774762
Wikipedia
Fleroxacin
ATC Codes
J01MA08 — Fleroxacin

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)270 dec °CPhysProp
logP0.24ROSS,DL ET AL. (1992) (ION-CORRECT)
Caco2 permeability-4.81ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.284 mg/mLALOGPS
logP0.3ALOGPS
logP1.12ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)5.44ChemAxon
pKa (Strongest Basic)6.06ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area64.09 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity90.84 m3·mol-1ChemAxon
Polarizability34.71 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-0169000000-c300db33eb5021a5c529

Taxonomy

Description
This compound 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Quinolines and derivatives
Sub Class
Quinoline carboxylic acids
Direct Parent
Quinoline carboxylic acids
Alternative Parents
N-arylpiperazines / Fluoroquinolones / Aminoquinolines and derivatives / Hydroquinolones / Haloquinolines / Hydroquinolines / Pyridinecarboxylic acids / Dialkylarylamines / N-methylpiperazines / Aryl fluorides
show 14 more
Substituents
Quinoline-3-carboxylic acid / Fluoroquinolone / N-arylpiperazine / Aminoquinoline / Haloquinoline / Dihydroquinolone / Dihydroquinoline / Pyridine carboxylic acid / Pyridine carboxylic acid or derivatives / Tertiary aliphatic/aromatic amine
show 32 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
quinolines, fluoroquinolone antibiotic (CHEBI:31810)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
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 segr...
Gene Name
TOP2A
Uniprot ID
P11388
Uniprot Name
DNA topoisomerase 2-alpha
Molecular Weight
174383.88 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Robinson MJ, Martin BA, Gootz TD, McGuirk PR, Osheroff N: Effects of novel fluoroquinolones on the catalytic activities of eukaryotic topoisomerase II: Influence of the C-8 fluorine group. Antimicrob Agents Chemother. 1992 Apr;36(4):751-6. [PubMed:1323952]
  3. Hussy P, Maass G, Tummler B, Grosse F, Schomburg U: Effect of 4-quinolones and novobiocin on calf thymus DNA polymerase alpha primase complex, topoisomerases I and II, and growth of mammalian lymphoblasts. Antimicrob Agents Chemother. 1986 Jun;29(6):1073-8. [PubMed:3015015]
Kind
Protein
Organism
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Dna topoisomerase type ii (atp-hydrolyzing) activity
Specific Function
DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, inc...
Gene Name
gyrA
Uniprot ID
P43700
Uniprot Name
DNA gyrase subunit A
Molecular Weight
97817.145 Da
References
  1. Naber KG: Fleroxacin overview. Chemotherapy. 1996 Mar;42 Suppl 1:1-9. [PubMed:8861529]
  2. Asahina Y, Iwase K, Iinuma F, Hosaka M, Ishizaki T: Synthesis and antibacterial activity of 1-(2-fluorovinyl)-7-substituted-4-quinolone-3-carboxylic acid derivatives, conformationally restricted analogues of fleroxacin. J Med Chem. 2005 May 5;48(9):3194-202. [PubMed:15857125]
Kind
Protein
Organism
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Dna topoisomerase type ii (atp-hydrolyzing) activity
Specific Function
Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule.
Gene Name
parC
Uniprot ID
P43702
Uniprot Name
DNA topoisomerase 4 subunit A
Molecular Weight
83366.24 Da
References
  1. Drlica K, Zhao X: DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev. 1997 Sep;61(3):377-92. [PubMed:9293187]
  2. Chaudhry U, Ray K, Bala M, Saluja D: Mutation patterns in gyrA and parC genes of ciprofloxacin resistant isolates of Neisseria gonorrhoeae from India. Sex Transm Infect. 2002 Dec;78(6):440-4. [PubMed:12473806]
  3. Lee JK, Lee YS, Park YK, Kim BS: Mutations in the gyrA and parC genes in ciprofloxacin-resistant clinical isolates of Acinetobacter baumannii in Korea. Microbiol Immunol. 2005;49(7):647-53. [PubMed:16034208]
  4. Leavis HL, Willems RJ, Top J, Bonten MJ: High-level ciprofloxacin resistance from point mutations in gyrA and parC confined to global hospital-adapted clonal lineage CC17 of Enterococcus faecium. J Clin Microbiol. 2006 Mar;44(3):1059-64. [PubMed:16517894]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
Curator comments
This drug is a fluoroquinolone, and these agents are known to inhibit CYP1A2.
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Zhang L, Wei MJ, Zhao CY, Qi HM: Determination of the inhibitory potential of 6 fluoroquinolones on CYP1A2 and CYP2C9 in human liver microsomes. Acta Pharmacol Sin. 2008 Dec;29(12):1507-14. doi: 10.1111/j.1745-7254.2008.00908.x. [PubMed:19026171]
  2. Shahzadi A, Javed I, Aslam B, Muhammad F, Asi MR, Ashraf MY, Zia-ur-Rahman: Therapeutic effects of ciprofloxacin on the pharmacokinetics of carbamazepine in healthy adult male volunteers. Pak J Pharm Sci. 2011 Jan;24(1):63-8. [PubMed:21190921]

Drug created on September 11, 2007 09:20 / Updated on October 01, 2018 15:59