Identification

Name
Rosoxacin
Accession Number
DB00817  (APRD00369)
Type
Small Molecule
Groups
Approved, Investigational
Description

Rosoxacin is a quinolone derivative antibiotic for the treatment of bacterial infection of respiratory tract, urinary tract, GI, CNS and immuno compromised patients. Rosoxacin is known to be effective against penicillin resistant strains and is a single dose orally administered drug, which avoids all complications of parenteral administration seen with penicillin, especially anaphylactic shock.

Structure
Thumb
Synonyms
  • Acrosoxacin
  • ROS
  • Rosoxacin
  • rosoxacina
  • Rosoxacine
  • Rosoxacino
  • Rosoxacinum
  • Roxadyl
External IDs
TO 133 / Win 35213
International/Other Brands
Eradacil (Sanofi-Aventis)
Categories
UNII
3Y1OT3J4NW
CAS number
40034-42-2
Weight
Average: 294.3047
Monoisotopic: 294.100442324
Chemical Formula
C17H14N2O3
InChI Key
XBPZXDSZHPDXQU-UHFFFAOYSA-N
InChI
InChI=1S/C17H14N2O3/c1-2-19-10-14(17(21)22)16(20)13-4-3-12(9-15(13)19)11-5-7-18-8-6-11/h3-10H,2H2,1H3,(H,21,22)
IUPAC Name
1-ethyl-4-oxo-7-(pyridin-4-yl)-1,4-dihydroquinoline-3-carboxylic acid
SMILES
CCN1C=C(C(O)=O)C(=O)C2=C1C=C(C=C2)C1=CC=NC=C1

Pharmacology

Indication

For the treatment of bacterial infection of respiratory tract, urinary tract, GI, CNS and immuno compromised patients.

Pharmacodynamics

Rosoxacin is a nonfluorinated quinolone antibiotic. Its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Rosoxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria.

Mechanism of action

Rosoxacin binds to and inhibits the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination.

TargetActionsOrganism
ADNA gyrase subunit B
inhibitor
Escherichia coli (strain K12)
ADNA topoisomerase 4 subunit A
inhibitor
Escherichia coli (strain K12)
Absorption
Not Available
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
  • Enteric bacteria and other eubacteria
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 Rosoxacin.
(S)-WarfarinThe therapeutic efficacy of (S)-Warfarin can be increased when used in combination with Rosoxacin.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be increased when used in combination with Rosoxacin.
3-isobutyl-1-methyl-7H-xanthineThe metabolism of 3-isobutyl-1-methyl-7H-xanthine can be decreased when combined with Rosoxacin.
4-hydroxycoumarinThe therapeutic efficacy of 4-hydroxycoumarin can be increased when used in combination with Rosoxacin.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Rosoxacin.
7-DeazaguanineThe metabolism of 7-Deazaguanine can be decreased when combined with Rosoxacin.
7,9-DimethylguanineThe metabolism of 7,9-Dimethylguanine can be decreased when combined with Rosoxacin.
8-azaguanineThe metabolism of 8-azaguanine can be decreased when combined with Rosoxacin.
8-chlorotheophyllineThe metabolism of 8-chlorotheophylline can be decreased when combined with Rosoxacin.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014955
KEGG Drug
D02305
PubChem Compound
287180
PubChem Substance
46508469
ChemSpider
253208
ChEBI
131715
ChEMBL
CHEMBL291157
Therapeutic Targets Database
DAP000929
PharmGKB
PA164776843
Wikipedia
Rosoxacin
ATC Codes
J01MB01 — Rosoxacin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedPreventionOral Leukoplakia1
Not AvailableNot Yet RecruitingHealth Services ResearchNicotine / Oxidative Stress1
Not AvailableRecruitingTreatmentPituitary Neoplasms1

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)290 °CPhysProp
water solubility0.0209 mg/mL at 25 °CMEYLAN,WM et al. (1996)
logP3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.102 mg/mLALOGPS
logP1.85ALOGPS
logP1.9ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)6.18ChemAxon
pKa (Strongest Basic)4.9ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area70.5 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity83.06 m3·mol-1ChemAxon
Polarizability30.8 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9953
Blood Brain Barrier+0.8044
Caco-2 permeable+0.6365
P-glycoprotein substrateNon-substrate0.5522
P-glycoprotein inhibitor INon-inhibitor0.8418
P-glycoprotein inhibitor IINon-inhibitor0.7855
Renal organic cation transporterNon-inhibitor0.8055
CYP450 2C9 substrateNon-substrate0.7741
CYP450 2D6 substrateNon-substrate0.8696
CYP450 3A4 substrateNon-substrate0.7172
CYP450 1A2 substrateNon-inhibitor0.7953
CYP450 2C9 inhibitorNon-inhibitor0.864
CYP450 2D6 inhibitorNon-inhibitor0.9328
CYP450 2C19 inhibitorNon-inhibitor0.8731
CYP450 3A4 inhibitorNon-inhibitor0.9181
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7267
Ames testNon AMES toxic0.8588
CarcinogenicityNon-carcinogens0.8638
BiodegradationNot ready biodegradable0.9751
Rat acute toxicity2.3043 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9583
hERG inhibition (predictor II)Non-inhibitor0.8496
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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

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
Phenylpyridines / Hydroquinolones / Hydroquinolines / Pyridinecarboxylic acids / Benzenoids / Vinylogous amides / Heteroaromatic compounds / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds
show 5 more
Substituents
Quinoline-3-carboxylic acid / 4-phenylpyridine / Dihydroquinolone / Dihydroquinoline / Pyridine carboxylic acid / Pyridine carboxylic acid or derivatives / Pyridine / Benzenoid / Heteroaromatic compound / Vinylogous amide
show 12 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Magnesium ion binding
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
gyrB
Uniprot ID
P0AES6
Uniprot Name
DNA gyrase subunit B
Molecular Weight
89949.195 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Zweerink MM, Edison A: Inhibition of Micrococcus luteus DNA gyrase by norfloxacin and 10 other quinolone carboxylic acids. Antimicrob Agents Chemother. 1986 Apr;29(4):598-601. [PubMed:3010848]
  4. Hirai K, Aoyama H, Suzue S, Irikura T, Iyobe S, Mitsuhashi S: Isolation and characterization of norfloxacin-resistant mutants of Escherichia coli K-12. Antimicrob Agents Chemother. 1986 Aug;30(2):248-53. [PubMed:3532944]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Escherichia coli (strain K12)
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. MukB stimulates th...
Gene Name
parC
Uniprot ID
P0AFI2
Uniprot Name
DNA topoisomerase 4 subunit A
Molecular Weight
83830.455 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Zweerink MM, Edison A: Inhibition of Micrococcus luteus DNA gyrase by norfloxacin and 10 other quinolone carboxylic acids. Antimicrob Agents Chemother. 1986 Apr;29(4):598-601. [PubMed:3010848]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
Curator comments
This drug is a quinolone derivative, 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. English BA, Dortch M, Ereshefsky L, Jhee S: Clinically significant psychotropic drug-drug interactions in the primary care setting. Curr Psychiatry Rep. 2012 Aug;14(4):376-90. doi: 10.1007/s11920-012-0284-9. [PubMed:22707017]
  3. 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 June 13, 2005 07:24 / Updated on November 02, 2018 04:50