Identification

Name
Cefacetrile
Accession Number
DB01414
Type
Small Molecule
Groups
Approved
Description

A derivative of 7-aminocephalosporanic acid.

Structure
Thumb
Synonyms
  • Cefacetrilo
  • Cefacetrilum
  • Cephacetrile
  • Vetrimast [veterinary]
International/Other Brands
Celospor (Ciba) / Celtol (Takeda)
Categories
UNII
FDM21QQ344
CAS number
10206-21-0
Weight
Average: 339.324
Monoisotopic: 339.052505853
Chemical Formula
C13H13N3O6S
InChI Key
RRYMAQUWDLIUPV-BXKDBHETSA-N
InChI
InChI=1S/C13H13N3O6S/c1-6(17)22-4-7-5-23-12-9(15-8(18)2-3-14)11(19)16(12)10(7)13(20)21/h9,12H,2,4-5H2,1H3,(H,15,18)(H,20,21)/t9-,12-/m1/s1
IUPAC Name
(6R,7R)-3-[(acetyloxy)methyl]-7-(2-cyanoacetamido)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
SMILES
[H][[email protected]]12SCC(COC(C)=O)=C(N1C(=O)[[email protected]]2NC(=O)CC#N)C(O)=O

Pharmacology

Indication

Cefacetrile is a broad-spectrum first generation cephalosporin antibiotic effective in Gram-positive and Gram-negative bacterial infections.

Structured Indications
Not Available
Pharmacodynamics

Cefacetrile is effective against many Gram-positive bacterial strains and somewhat less effective against Gram-negative species. It works by inhibition of bacterial cell wall synthesis. It attains high serum levels and is excreted quickly via the urine.

Mechanism of action

In vitro tests demonstrate that the bactericidal action of cephalosporins results from inhibition of cell wall synthesis. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins.

TargetActionsOrganism
APenicillin-binding protein 1A
inhibitor
Escherichia coli (strain K12)
APenicillin-binding protein 1B
inhibitor
Escherichia coli (strain K12)
Absorption
Not Available
Volume of distribution

Vd of 0.2 to 0.5L/.kg

Protein binding

23 to 38%

Metabolism
Not Available
Route of elimination
Not Available
Half life

1.2 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcenocoumarolCefacetrile may increase the anticoagulant activities of Acenocoumarol.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Cefacetrile.Investigational
ClorindioneCefacetrile may increase the anticoagulant activities of Clorindione.Experimental
DicoumarolCefacetrile may increase the anticoagulant activities of Dicoumarol.Approved
DiphenadioneCefacetrile may increase the anticoagulant activities of Diphenadione.Experimental
Ethyl biscoumacetateCefacetrile may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FluindioneCefacetrile may increase the anticoagulant activities of Fluindione.Investigational
PhenindioneCefacetrile may increase the anticoagulant activities of Phenindione.Approved, Investigational
PhenprocoumonCefacetrile may increase the anticoagulant activities of Phenprocoumon.Approved, Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Cefacetrile.Approved
ProbenecidThe serum concentration of Cefacetrile can be increased when it is combined with Probenecid.Approved
TeriflunomideThe serum concentration of Cefacetrile can be increased when it is combined with Teriflunomide.Approved
TioclomarolCefacetrile may increase the anticoagulant activities of Tioclomarol.Experimental
WarfarinCefacetrile may increase the anticoagulant activities of Warfarin.Approved
Food Interactions
Not Available

References

Synthesis Reference

Bickel, H., Bosshardt, R., Fechtig, B., Schenker, K. and Urech, J.; U.S. Patent 3,483,197; December 9,1969; assigned to Ciba Corporation.

General References
Not Available
External Links
Human Metabolome Database
HMDB15484
KEGG Drug
D07629
PubChem Compound
91562
PubChem Substance
46504767
ChemSpider
82675
ChEBI
135437
ChEMBL
CHEMBL2110602
Therapeutic Targets Database
DAP001172
PharmGKB
PA164776752
Wikipedia
Cefacetrile
ATC Codes
J01DB10 — Cefacetrile

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)168-170Bickel, H., Bosshardt, R., Fechtig, B., Schenker, K. and Urech, J.; U.S. Patent 3,483,197; December 9,1969; assigned to Ciba Corporation.
logP-0.45HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility2.43 mg/mLALOGPS
logP-0.52ALOGPS
logP-1.8ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)3.31ChemAxon
pKa (Strongest Basic)-6.2ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area136.8 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity77.51 m3·mol-1ChemAxon
Polarizability31.32 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9435
Blood Brain Barrier-0.9965
Caco-2 permeable-0.754
P-glycoprotein substrateSubstrate0.7774
P-glycoprotein inhibitor INon-inhibitor0.7686
P-glycoprotein inhibitor IINon-inhibitor0.9626
Renal organic cation transporterNon-inhibitor0.9013
CYP450 2C9 substrateNon-substrate0.7919
CYP450 2D6 substrateNon-substrate0.823
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.8122
CYP450 2C9 inhibitorNon-inhibitor0.8282
CYP450 2D6 inhibitorNon-inhibitor0.9145
CYP450 2C19 inhibitorNon-inhibitor0.8132
CYP450 3A4 inhibitorNon-inhibitor0.9152
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8735
Ames testNon AMES toxic0.6895
CarcinogenicityNon-carcinogens0.9237
BiodegradationNot ready biodegradable0.9705
Rat acute toxicity1.8811 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9933
hERG inhibition (predictor II)Non-inhibitor0.9062
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 cephalosporin 3'-esters. These are cephalosporins that are esterified at the 3'-position.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Lactams
Sub Class
Beta lactams
Direct Parent
Cephalosporin 3'-esters
Alternative Parents
N-acyl-alpha amino acids and derivatives / 1,3-thiazines / Dicarboxylic acids and derivatives / Tertiary carboxylic acid amides / Secondary carboxylic acid amides / Azetidines / Carboxylic acid esters / Thiohemiaminal derivatives / Azacyclic compounds / Nitriles
show 6 more
Substituents
Cephalosporin 3'-ester / N-acyl-alpha amino acid or derivatives / Alpha-amino acid or derivatives / Meta-thiazine / Dicarboxylic acid or derivatives / Tertiary carboxylic acid amide / Azetidine / Carboxamide group / Carboxylic acid ester / Secondary carboxylic acid amide
show 17 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
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 str...
Gene Name
mrcA
Uniprot ID
P02918
Uniprot Name
Penicillin-binding protein 1A
Molecular Weight
93635.545 Da
References
  1. Yotsuji A, Mitsuyama J, Hori R, Yasuda T, Saikawa I, Inoue M, Mitsuhashi S: Mechanism of action of cephalosporins and resistance caused by decreased affinity for penicillin-binding proteins in Bacteroides fragilis. Antimicrob Agents Chemother. 1988 Dec;32(12):1848-53. [PubMed:3266730]
  2. Truesdell SE, Zurenko GE, Laborde AL: Interaction of cephalosporins with penicillin-binding proteins of methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother. 1989 Apr;23 Suppl D:13-9. [PubMed:2722720]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
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 str...
Gene Name
mrcB
Uniprot ID
P02919
Uniprot Name
Penicillin-binding protein 1B
Molecular Weight
94291.875 Da
References
  1. Truesdell SE, Zurenko GE, Laborde AL: Interaction of cephalosporins with penicillin-binding proteins of methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother. 1989 Apr;23 Suppl D:13-9. [PubMed:2722720]
  2. Yotsuji A, Mitsuyama J, Hori R, Yasuda T, Saikawa I, Inoue M, Mitsuhashi S: Mechanism of action of cephalosporins and resistance caused by decreased affinity for penicillin-binding proteins in Bacteroides fragilis. Antimicrob Agents Chemother. 1988 Dec;32(12):1848-53. [PubMed:3266730]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
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:11909604]
  2. Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. [PubMed:10411577]
  3. 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:12005172]
  4. 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:15618660]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
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, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
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:11909604]
  2. Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. [PubMed:10411577]
  3. 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:12005172]
  4. 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:15618660]

Drug created on July 23, 2007 06:31 / Updated on November 09, 2017 02:59