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Identification
Name Cefoperazone
Accession Number DB01329
Type small molecule
Groups approved
Description

Semisynthetic broad-spectrum cephalosporin with a tetrazolyl moiety that is resistant to beta-lactamase. It has been proposed especially against Pseudomonas infections.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Cefoperazono [inn-spanish]
Cefoperazonum [inn-latin]
Salts Not Available
Brand names
Name Company
Cefobid
Brand mixtures Not Available
Categories
  • Anti-Bacterial Agents
  • Antibacterial Agents
  • Cephalosporins
CAS number 62893-19-0
Weight Average: 645.667
Monoisotopic: 645.142400265
Chemical Formula C25H27N9O8S2
InChI Key InChIKey=GCFBRXLSHGKWDP-WTKTZPJXSA-N
InChI
InChI=1S/C25H27N9O8S2/c1-3-32-8-9-33(21(39)20(32)38)24(42)27-15(12-4-6-14(35)7-5-12)18(36)26-16-19(37)34-17(23(40)41)13(10-43-22(16)34)11-44-25-28-29-30-31(25)2/h4-7,15-16,22,35H,3,8-11H2,1-2H3,(H,26,36)(H,27,42)(H,40,41)/t15?,16-,22-/m1/s1
Plain Text
IUPAC Name
(6R,7R)-7-(2-{[(4-ethyl-2,3-dioxopiperazin-1-yl)carbonyl]amino}-2-(4-hydroxyphenyl)acetamido)-3-{[(1-methyl-1H-1,2,3,4-tetrazol-5-yl)sulfanyl]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
SMILES
[H][C@]12SCC(CSC3=NN=NN3C)=C(N1C(=O)[C@H]2NC(=O)C(NC(=O)N1CCN(CC)C(=O)C1=O)C1=CC=C(O)C=C1)C(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenols and Derivatives
  • Phenethylamines
  • Cephalosporins
Substructures
  • Ethers
  • Hydroxy Compounds
  • Acetates
  • Phenols and Derivatives
  • Amino Ketones
  • Carboxylic Acids and Derivatives
  • Piperazines
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Ureas and Derivatives
  • Beta Lactams
  • Enamines
  • Tetrazoles
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Cephalosporins
  • Lactams
  • Azetidines
  • Cyanamides
  • Phenyl Esters
Pharmacology
Indication For the treatment of bacterial infections caused by susceptible microorganisms.
Pharmacodynamics Cefoperazone is a third generation cephalosporin antibiotic. Cefoperazone exerts its bactericidal effect by inhibiting the bacterial cell wall synthesis
Mechanism of action Like all beta-lactam antibiotics, cefoperazone binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, causing the inhibition of the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins.
Absorption Not Available
Volume of distribution Not Available
Protein binding The degree of reversible protein binding varies with the serum concentration from 93% at 25 mcg/mL to 90% at 250 mcg/mL and 82% at 500 mcg/mL. Cefotetan is 88% plasma protein bound.
Metabolism No significant quanitity of metabolites have been identified in urine.
Route of elimination Cefoperazone is excreted mainly in the bile.
Half life The mean serum half-life is approximately 2.0 hours, independent of the route of administration.
Clearance Not Available
Toxicity Symptoms of overdose include blood in the urine, diarrhea, nausea, upper abdominal pain, and vomiting.
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Pfizer laboratories div pfizer inc
  • Pfizer inc
Packagers
Dosage forms
Form Route Strength
Powder, for solution Intramuscular
Powder, for solution Intravenous
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 167-171 °C PhysProp
logP -0.74 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 2.86e-01 g/l ALOGPS
logP -0.11 ALOGPS
logP -0.9 ChemAxon
logS -3.4 ALOGPS
pKa (strongest acidic) 3.38 ChemAxon
pKa (strongest basic) -1.7 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 11 ChemAxon
hydrogen donor count 4 ChemAxon
polar surface area 220.26 ChemAxon
rotatable bond count 9 ChemAxon
refractivity 169.06 ChemAxon
polarizability 62.62 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Jones RN, Barry AL: Cefoperazone: a review of its antimicrobial spectrum, beta-lactamase stability, enzyme inhibition, and other in vitro characteristics. Rev Infect Dis. 1983 Mar-Apr;5 Suppl 1:S108-26. Pubmed
External Links
Resource Link
KEGG Compound C06883 Link_out
PubChem Compound 44185 Link_out
PubChem Substance 46504543 Link_out
ChemSpider 40204 Link_out
ChEBI 3493 Link_out
ChEMBL 3493 Link_out
Therapeutic Targets Database DAP000450 Link_out
PharmGKB PA448849 Link_out
Wikipedia http://en.wikipedia.org/wiki/Cefoperazone Link_out
ATC Codes
  • J01DD12
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (29 MB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Amikacin Increased risk of nephrotoxicity
Gentamicin Increased risk of nephrotoxicity
Netilmicin Increased risk of nephrotoxicity
Tobramycin Increased risk of nephrotoxicity
Food Interactions Not Available
Targets

1. Peptidoglycan synthetase ftsI

Pharmacological action: yes
Actions: inhibitor

Cell wall formation. Essential for the formation of a septum of the murein sacculus. Synthesis of cross-linked peptidoglycan from the lipid intermediates

Organism class: bacterial
UniProt ID: P0AD68 Link_out
Gene: ftsI
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Matsubara N, Minami S, Matsuhashi M, Takaoka M, Mitsuhashi S: Affinity of cefoperazone for penicillin-binding proteins. Antimicrob Agents Chemother. 1980 Jul;18(1):195-9. Pubmed

2. Penicillin-binding protein 1B

Pharmacological action: yes
Actions: inhibitor

Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits)

Organism class: bacterial
UniProt ID: P02919 Link_out
Gene: mrcB
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Matsubara N, Minami S, Matsuhashi M, Takaoka M, Mitsuhashi S: Affinity of cefoperazone for penicillin-binding proteins. Antimicrob Agents Chemother. 1980 Jul;18(1):195-9. Pubmed

3. Penicillin-binding protein 2

Pharmacological action: yes
Actions: inhibitor

Cell wall formation; PBP-2 is responsible for the determination of the rod shape of the cell. Its synthesize cross- linked peptidoglycan from the lipid intermediates

Organism class: bacterial
UniProt ID: P0AD65 Link_out
Gene: mrdA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Matsubara N, Minami S, Matsuhashi M, Takaoka M, Mitsuhashi S: Affinity of cefoperazone for penicillin-binding proteins. Antimicrob Agents Chemother. 1980 Jul;18(1):195-9. Pubmed

4. Penicillin-binding protein 1A

Pharmacological action: yes
Actions: inhibitor

Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits) (By similarity)

Organism class: bacterial
UniProt ID: Q07806 Link_out
Gene: mrcA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Matsubara N, Minami S, Matsuhashi M, Takaoka M, Mitsuhashi S: Affinity of cefoperazone for penicillin-binding proteins. Antimicrob Agents Chemother. 1980 Jul;18(1):195-9. Pubmed

5. Penicillin-binding protein 1B

Pharmacological action: yes
Actions: inhibitor
Organism class: bacterial
UniProt ID: Q9X6W0 Link_out
Gene: ponB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Matsubara N, Minami S, Matsuhashi M, Takaoka M, Mitsuhashi S: Affinity of cefoperazone for penicillin-binding proteins. Antimicrob Agents Chemother. 1980 Jul;18(1):195-9. Pubmed

6. D-alanyl-D-alanine carboxypeptidase dacC

Pharmacological action: yes
Actions: inhibitor

Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors

Organism class: bacterial
UniProt ID: P08506 Link_out
Gene: dacC Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Matsubara N, Minami S, Matsuhashi M, Takaoka M, Mitsuhashi S: Affinity of cefoperazone for penicillin-binding proteins. Antimicrob Agents Chemother. 1980 Jul;18(1):195-9. Pubmed

7. Penicillin-binding protein 1A

Pharmacological action: yes
Actions: inhibitor

Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits)

Organism class: bacterial
UniProt ID: P02918 Link_out
Gene: mrcA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Matsubara N, Minami S, Matsuhashi M, Takaoka M, Mitsuhashi S: Affinity of cefoperazone for penicillin-binding proteins. Antimicrob Agents Chemother. 1980 Jul;18(1):195-9. Pubmed

8. Penicillin-binding protein 5 precursor

Pharmacological action: yes
Actions: inhibitor

Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors

Organism class: bacterial
UniProt ID: P0AEB2 Link_out
Gene: dacA
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Matsubara N, Minami S, Matsuhashi M, Takaoka M, Mitsuhashi S: Affinity of cefoperazone for penicillin-binding proteins. Antimicrob Agents Chemother. 1980 Jul;18(1):195-9. Pubmed

9. Penicillin-binding protein 4

Pharmacological action: yes
Actions: inhibitor

Not involved in transpeptidation but exclusively catalyzes a DD-carboxypeptidase and DD-endopeptidase reaction

Organism class: bacterial
UniProt ID: P24228 Link_out
Gene: dacB
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Matsubara N, Minami S, Matsuhashi M, Takaoka M, Mitsuhashi S: Affinity of cefoperazone for penicillin-binding proteins. Antimicrob Agents Chemother. 1980 Jul;18(1):195-9. Pubmed
Transporters

1. Solute carrier family 22 member 6

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out
Gene: hROAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed
  2. Jung KY, Takeda M, Shimoda M, Narikawa S, Tojo A, Kim DK, Chairoungdua A, Choi BK, Kusuhara H, Sugiyama Y, Sekine T, Endou H: Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1. Life Sci. 2002 Mar 8;70(16):1861-74. Pubmed
  3. Uwai Y, Saito H, Inui K: Rat renal organic anion transporter rOAT1 mediates transport of urinary-excreted cephalosporins, but not of biliary-excreted cefoperazone. Drug Metab Pharmacokinet. 2002;17(2):125-9. Pubmed

2. Solute carrier family 22 member 8

Actions: inhibitor

Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone- 3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA)

UniProt ID: Q8TCC7 Link_out
Gene: SLC22A8 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed
  2. Jung KY, Takeda M, Shimoda M, Narikawa S, Tojo A, Kim DK, Chairoungdua A, Choi BK, Kusuhara H, Sugiyama Y, Sekine T, Endou H: Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1. Life Sci. 2002 Mar 8;70(16):1861-74. Pubmed
  3. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. Pubmed

3. Solute carrier family 22 member 11

Actions: inhibitor

Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds

UniProt ID: Q9NSA0 Link_out
Gene: SLC22A11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed

4. Solute carrier family 22 member 7

Actions: inhibitor

Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha- ketoglutarate

UniProt ID: Q9Y694 Link_out
Gene: SLC22A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Khamdang S, Takeda M, Babu E, Noshiro R, Onozato ML, Tojo A, Enomoto A, Huang XL, Narikawa S, Anzai N, Piyachaturawat P, Endou H: Interaction of human and rat organic anion transporter 2 with various cephalosporin antibiotics. Eur J Pharmacol. 2003 Mar 28;465(1-2):1-7. Pubmed
  2. Kobayashi Y, Ohshiro N, Shibusawa A, Sasaki T, Tokuyama S, Sekine T, Endou H, Yamamoto T: Isolation, characterization and differential gene expression of multispecific organic anion transporter 2 in mice. Mol Pharmacol. 2002 Jul;62(1):7-14. Pubmed
  3. Sekine T, Cha SH, Tsuda M, Apiwattanakul N, Nakajima N, Kanai Y, Endou H: Identification of multispecific organic anion transporter 2 expressed predominantly in the liver. FEBS Lett. 1998 Jun 12;429(2):179-82. Pubmed
Carriers

1. Serum albumin

Actions: other/unknown

Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood

UniProt ID: P02768 Link_out
Gene: ALB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Liu LS, Zhang YY, Wang XP: [The reaction mechanism between cefoperazone and human serum albumin] Guang Pu Xue Yu Guang Pu Fen Xi. 2005 Sep;25(9):1490-2. Pubmed
  2. Gulian JM, Dalmasso C, Gonard V: Interaction of beta-lactam antibiotics on bilirubin-albumin complex: comparison by three methods, total bilirubin, unbound bilirubin and erythrocyte-bound bilirubin. Chemotherapy. 1990;36(2):91-7. Pubmed
  3. Leggett JE, Craig WA: Enhancing effect of serum ultrafiltrate on the activity of cephalosporins against gram-negative bacilli. Antimicrob Agents Chemother. 1989 Jan;33(1):35-40. Pubmed
  4. Robertson A, Fink S, Karp W: Effect of cephalosporins on bilirubin-albumin binding. J Pediatr. 1988 Feb;112(2):291-4. Pubmed
  5. Nerli B, Farruggia B, Pico G: A comparative study of the binding characteristics of ceftriaxone, cefoperazone and cefsulodin to human serum albumin. Biochem Mol Biol Int. 1996 Nov;40(4):823-31. Pubmed
Comments
Drug created on June 30, 2007 11:50 / Updated on February 08, 2013 16:20