DrugBank: Cefacetrile (DB01414)

targets (2) transporters (2) carriers (1)

Identification

Name

Cefacetrile

Accession Number

DB01414

Type

small molecule

Groups

approved

Description

A derivative of 7-aminocephalosporanic acid.

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

7-Cyanacetylamino-cephalosporansaeure
Cefacetrilo [inn-spanish]
Cefacetrilum [inn-latin]
Cephacetrile

Brand names

Celospor
Celtol
Cristacef

Brand name mixtures

Not Available

Categories

Anti-Bacterial Agents
Cephalosporins

CAS number

10206-21-0

Weight

Average: 339.324
Monoisotopic: 339.052505853

Chemical Formula

C₁₃H₁₃N₃O₆S

InChI Key

InChIKey=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

Plain Text

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][C@]12SCC(COC(C)=O)=C(N1C(=O)[C@H]2NC(=O)CC#N)C(O)=O

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Ethers
Cephalosporins

Substructures

Carboxylic Acids and Derivatives
Hydroxy Compounds
Acetates
Amino Ketones
Nitriles and Derivatives
Ethers
Aliphatic and Aryl Amines
Beta Lactams
Enamines
Cyanides
Heterocyclic compounds
Carboxamides and Derivatives
Cephalosporins
Lactams
Azetidines

Pharmacology

Indication

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

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.

Absorption

Not Available

Volume of distribution

Vd of 0.2 to 0.5L/.kg

Protein binding

23 to 38%

Metabolism

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

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	-0.45 [HANSCH,C ET AL. (1995)]	PhysProp

Predicted Properties

Property	Value	Source
water solubility	2.43e+00 g/l	ALOGPS
logP	-0.52	ALOGPS
logP	-1.78	ChemAxon Molconvert
logS	-2.15	ALOGPS
pKa	6.22	ChemAxon Molconvert
hydrogen acceptor count	6	ChemAxon Molconvert
hydrogen donor count	2	ChemAxon Molconvert
polar surface area	136.80	ChemAxon Molconvert
rotatable bond count	6	ChemAxon Molconvert
refractivity	77.51	ChemAxon Molconvert
polarizability	31.32	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Drug	D07629
PubChem Compound	91562
PubChem Substance	46504767
ChemSpider	82675
Therapeutic Targets Database	DAP001172
Drug Product Database	0
Wikipedia	http://en.wikipedia.org/wiki/Cefacetrile

ATC Codes

J01DB10

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Drug	Interaction

Food Interactions

Not Available

Targets
1. 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 Gene: mrcA Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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 Gene: mrcB Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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

Targets

1. 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:

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
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

2. Penicillin-binding protein 1B

Pharmacological action: yes
Actions: inhibitor

Organism class: bacterial
UniProt ID: P02919 Link_out

Gene: mrcB
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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

Transporters
1. Solute carrier family 22 member 6 Actions: substrate, inhibitor UniProt ID: Q4U2R8 Gene: hROAT1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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 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: substrate, 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 Gene: SLC22A8 Protein Sequence: FASTA SNPs: SNPJam Report References: 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 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 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 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

Transporters

1. Solute carrier family 22 member 6

Actions: substrate, inhibitor
UniProt ID: Q4U2R8 Link_out

Gene: hROAT1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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
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
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: substrate, 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:

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
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
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
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

Carriers
1. Serum albumin 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 Gene: ALB Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Bratlid D, Bergan T: Displacement of albumin-bound antimicrobial agents by bilirubin. Pharmacology. 1976;14(5):464-72. Pubmed Decroix MO, Zini R, Chaumeil JC, Tillement JP: Cefazolin serum protein binding and its inhibition by bilirubin, fatty acids and other drugs. Biochem Pharmacol. 1988 Jul 15;37(14):2807-14. Pubmed Ichimura F, Matsushita R, Tsuji A, Deguchi Y: Mutual interaction between bilirubin and cefazolin in binding to human serum albumin. J Pharm Sci. 1990 Nov;79(11):1041-2. Pubmed

Carriers

1. Serum albumin

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

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Bratlid D, Bergan T: Displacement of albumin-bound antimicrobial agents by bilirubin. Pharmacology. 1976;14(5):464-72. Pubmed
Decroix MO, Zini R, Chaumeil JC, Tillement JP: Cefazolin serum protein binding and its inhibition by bilirubin, fatty acids and other drugs. Biochem Pharmacol. 1988 Jul 15;37(14):2807-14. Pubmed
Ichimura F, Matsushita R, Tsuji A, Deguchi Y: Mutual interaction between bilirubin and cefazolin in binding to human serum albumin. J Pharm Sci. 1990 Nov;79(11):1041-2. Pubmed

Comments

Drug created on July 23, 2007 06:31 / Updated on December 27, 2010 09:53

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.