Banner
targets (2) enzymes (1)
for drugs
Identification
Name Temafloxacin
Accession Number DB01405
Type small molecule
Groups withdrawn
Description

Temafloxacin is a fluoroquinolone antibiotic drug which was withdrawn from sale in the U.S. shortly after its approval in 1992 because of serious adverse reactions resulting in three deaths. [Wikipedia]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Temafloxacin hydrochloride
  • Temafloxacina [spanish]
  • Temafloxacine [french]
  • Temafloxacinum [latin]
Synonyms
Temafloxacin hydrochloride
Temafloxacina [spanish]
Temafloxacine [french]
Temafloxacinum [latin]
Salts Not Available
Brand names
Name Company
Omniflox
Brand mixtures Not Available
Categories
  • Anti-Bacterial Agents
CAS number 108319-06-8
Weight Average: 417.3811
Monoisotopic: 417.130026072
Chemical Formula C21H18F3N3O3
InChI Key InChIKey=QKDHBVNJCZBTMR-UHFFFAOYSA-N
InChI
InChI=1S/C21H18F3N3O3/c1-11-9-26(5-4-25-11)19-8-18-13(7-16(19)24)20(28)14(21(29)30)10-27(18)17-3-2-12(22)6-15(17)23/h2-3,6-8,10-11,25H,4-5,9H2,1H3,(H,29,30)
Plain Text
IUPAC Name
1-(2,4-difluorophenyl)-6-fluoro-7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
SMILES
CC1CN(CCN1)C1=C(F)C=C2C(=O)C(=CN(C2=C1)C1=C(F)C=C(F)C=C1)C(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Fluoroquinolones and Quinolones
  • Aminoquinolines and Derivatives
Substructures
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Pyridines and Derivatives
  • Piperazines
  • Fluoroquinolones and Quinolones
  • Benzene and Derivatives
  • Aminoquinolines and Derivatives
  • Carboxylic Acids and Derivatives
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • (Iso)quinolines and Derivatives
  • Aryl Halides
  • Anilines
Pharmacology
Indication For the treatment of lower respiratory tract infections, genital and urinary infections like prostatitis, and skin infections.
Pharmacodynamics Temafloxacin (marketed by Abbott Laboratories as Omniflox), is a fluoroquinolone antibiotic drug which was withdrawn from sale in the U.S. shortly after its approval in 1992 because of serious adverse reactions resulting in three deaths. Flouroquinolones such as lomefloxacin possess excellent activity against gram-negative aerobic bacteria such as E.coli and Neisseria gonorrhoea as well as gram-positive bacteria including S. pneumoniae and Staphylococcus aureus. They also posses effective activity against shigella, salmonella, campylobacter, gonococcal organisms, and multi drug resistant pseudomonas and enterobacter.
Mechanism of action The bactericidal action of temafloxacin results from interference with the activity of the bacterial enzymes DNA gyrase and topoisomerase IV, which are needed for the transcription and replication of bacterial DNA. DNA gyrase appears to be the primary quinolone target for gram-negative bacteria. Topoisomerase IV appears to be the preferential target in gram-positive organisms. Interference with these two topoisomerases results in strand breakage of the bacterial chromosome, supercoiling, and resealing. As a result DNA replication and transcription is inhibited.
Absorption Studies in healthy volunteers indicate that the average bioavailability of temafloxacin exceeds 90%, with little intersubject variability.
Volume of distribution Not Available
Protein binding Not Available
Metabolism Hepatic.
Route of elimination Not Available
Half life Approximately 8 hours in patients with normal renal function.
Clearance Not Available
Toxicity Severe adverse reactions, including allergic reactions and hemolytic anemia, developed in about fifty patients during the first four months of its use, leading to three patient deaths
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
logP -0.20 [BIOBYTE (1995)] PhysProp
Predicted Properties
Property Value Source
water solubility 1.44e-02 g/l ALOGPS
logP 0.94 ALOGPS
logP 1.08 ChemAxon Molconvert
logS -4.5 ALOGPS
pKa 0 ChemAxon Molconvert
hydrogen acceptor count 6 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 72.88 ChemAxon Molconvert
rotatable bond count 3 ChemAxon Molconvert
refractivity 104.53 ChemAxon Molconvert
polarizability 39.7 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D02469 Link_out
PubChem Compound 60021 Link_out
PubChem Substance 46508032 Link_out
ChemSpider 54143 Link_out
Wikipedia http://en.wikipedia.org/wiki/Temafloxacin Link_out
ATC Codes
  • J01MA05
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Calcium Formation of non-absorbable complexes
Iron Dextran Formation of non-absorbable complexes
Magnesium Formation of non-absorbable complexes
Food Interactions Not Available
Targets

1. DNA gyrase subunit A

Pharmacological action: yes
Actions: inhibitor

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, including catenanes and knotted rings

Organism class: bacterial
UniProt ID: P43700 Link_out
Gene: gyrA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Frank KE, Devasthale PV, Gentry EJ, Ravikumar VT, Keschavarz-Shokri A, Mitscher LA, Nilius A, Shen LL, Shawar R, Baker WR: A simple, inexpensive apparatus for performance of preparative scale solution phase multiple parallel synthesis of drug analogs. II. Biological evaluation of a retrospective library of quinolone antiinfective agents. Comb Chem High Throughput Screen. 1998 Jun;1(2):89-99. Pubmed
  4. Nakanishi N, Yoshida S, Wakebe H, Inoue M, Yamaguchi T, Mitsuhashi S: Mechanisms of clinical resistance to fluoroquinolones in Staphylococcus aureus. Antimicrob Agents Chemother. 1991 Dec;35(12):2562-7. Pubmed
  5. Nakanishi N, Yoshida S, Wakebe H, Inoue M, Mitsuhashi S: Mechanisms of clinical resistance to fluoroquinolones in Enterococcus faecalis. Antimicrob Agents Chemother. 1991 Jun;35(6):1053-9. Pubmed
  6. Appelbaum PC: Mechanisms and frequency of resistance to temafloxacin. Am J Med. 1991 Dec 30;91(6A):27S-30S. Pubmed

2. DNA topoisomerase 4 subunit A

Pharmacological action: yes
Actions: inhibitor

Topoisomerase IV is essential for chromosome segregation. It has relaxation of supercoiled DNA activity. Performs the decatenation events required during the replication of a circular DNA molecule

Organism class: bacterial
UniProt ID: P43702 Link_out
Gene: parC
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Nakanishi N, Yoshida S, Wakebe H, Inoue M, Yamaguchi T, Mitsuhashi S: Mechanisms of clinical resistance to fluoroquinolones in Staphylococcus aureus. Antimicrob Agents Chemother. 1991 Dec;35(12):2562-7. Pubmed
  4. Nakanishi N, Yoshida S, Wakebe H, Inoue M, Mitsuhashi S: Mechanisms of clinical resistance to fluoroquinolones in Enterococcus faecalis. Antimicrob Agents Chemother. 1991 Jun;35(6):1053-9. Pubmed
  5. Appelbaum PC: Mechanisms and frequency of resistance to temafloxacin. Am J Med. 1991 Dec 30;91(6A):27S-30S. Pubmed
Enzymes

1. Cytochrome P450 1A2

Actions: substrate, inhibitor

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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on July 13, 2007 14:27 / Updated on February 14, 2012 11:47