Identification

Name
Cefonicid
Accession Number
DB01328
Type
Small Molecule
Groups
Approved, Investigational
Description

A second-generation cephalosporin administered intravenously or intramuscularly. Its bactericidal action results from inhibition of cell wall synthesis. It is used for urinary tract infections, lower respiratory tract infections, and soft tissue and bone infections. [PubChem]

Structure
Thumb
Synonyms
  • (6R,7R)-7-{[(2R)-2-hydroxy-2-phenylacetyl]amino}-8-oxo-3-({[1-(sulfomethyl)-1H-tetrazol-5-yl]sulfanyl}methyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  • Cefonicid
  • Cefonicido
  • Cefonicidum
Product Ingredients
IngredientUNIICASInChI Key
Cefonicid sodiumF74MFL78A161270-78-8NAXFZVGOZUWLEP-RFXDPDBWSA-L
International/Other Brands
Monocid / Praticef
Categories
UNII
6532B86WFG
CAS number
61270-58-4
Weight
Average: 542.566
Monoisotopic: 542.034823652
Chemical Formula
C18H18N6O8S3
InChI Key
DYAIAHUQIPBDIP-AXAPSJFSSA-N
InChI
InChI=1S/C18H18N6O8S3/c25-13(9-4-2-1-3-5-9)14(26)19-11-15(27)24-12(17(28)29)10(6-33-16(11)24)7-34-18-20-21-22-23(18)8-35(30,31)32/h1-5,11,13,16,25H,6-8H2,(H,19,26)(H,28,29)(H,30,31,32)/t11-,13-,16-/m1/s1
IUPAC Name
(6R,7R)-7-[(2R)-2-hydroxy-2-phenylacetamido]-8-oxo-3-({[1-(sulfomethyl)-1H-1,2,3,4-tetrazol-5-yl]sulfanyl}methyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
SMILES
[H][[email protected]]12SCC(CSC3=NN=NN3CS(O)(=O)=O)=C(N1C(=O)[[email protected]]2NC(=O)[[email protected]](O)C1=CC=CC=C1)C(O)=O

Pharmacology

Indication

For the treatment of bacterial infections caused by susceptible microorganisms.

Structured Indications
Not Available
Pharmacodynamics

Cefonicid is a second-generation cephalosporin administered intravenously or intramuscularly. Its bactericidal action results from inhibition of cell wall synthesis. It is used for urinary tract infections, lower respiratory tract infections, and soft tissue and bone infections.

Mechanism of action

Cefonicid, like the penicillins, is a beta-lactam antibiotic. 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)
APeptidoglycan synthase FtsI
inhibitor
Escherichia coli (strain K12)
APenicillin-binding protein 1B
inhibitor
Escherichia coli (strain K12)
AD-alanyl-D-alanine carboxypeptidase DacB
inhibitor
Escherichia coli (strain K12)
APenicillin-binding protein 2
inhibitor
Escherichia coli (strain K12)
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

98% bound to plasma proteins.

Metabolism

Not metabolized.

Route of elimination
Not Available
Half life

4.5 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
AcenocoumarolCefonicid may increase the anticoagulant activities of Acenocoumarol.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Cefonicid.Investigational
ClorindioneCefonicid may increase the anticoagulant activities of Clorindione.Experimental
DicoumarolCefonicid may increase the anticoagulant activities of Dicoumarol.Approved
DiphenadioneCefonicid may increase the anticoagulant activities of Diphenadione.Experimental
Ethyl biscoumacetateCefonicid may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FluindioneCefonicid may increase the anticoagulant activities of Fluindione.Investigational
PhenindioneCefonicid may increase the anticoagulant activities of Phenindione.Approved, Investigational
PhenprocoumonCefonicid may increase the anticoagulant activities of Phenprocoumon.Approved, Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Cefonicid.Approved
ProbenecidThe serum concentration of Cefonicid can be increased when it is combined with Probenecid.Approved
TioclomarolCefonicid may increase the anticoagulant activities of Tioclomarol.Experimental
WarfarinCefonicid may increase the anticoagulant activities of Warfarin.Approved
Food Interactions
Not Available

References

Synthesis Reference

Theodore John Polansky, "Crystalline benzathine salt of cefonicid and its preparation." U.S. Patent US5705496, issued October, 1992.

US5705496
General References
Not Available
External Links
Human Metabolome Database
HMDB15423
KEGG Compound
C06882
PubChem Compound
43594
PubChem Substance
46505699
ChemSpider
39734
ChEBI
3491
ChEMBL
CHEMBL1601
Therapeutic Targets Database
DAP001173
PharmGKB
PA164743021
ATC Codes
J01DC06 — Cefonicid

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.895 mg/mLALOGPS
logP-0.71ALOGPS
logP-2.5ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)-1.4ChemAxon
pKa (Strongest Basic)-2.1ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area204.91 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity136.58 m3·mol-1ChemAxon
Polarizability47.96 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9607
Blood Brain Barrier-0.9728
Caco-2 permeable-0.6466
P-glycoprotein substrateSubstrate0.6941
P-glycoprotein inhibitor INon-inhibitor0.7169
P-glycoprotein inhibitor IINon-inhibitor0.92
Renal organic cation transporterNon-inhibitor0.8219
CYP450 2C9 substrateNon-substrate0.84
CYP450 2D6 substrateNon-substrate0.8057
CYP450 3A4 substrateSubstrate0.5056
CYP450 1A2 substrateNon-inhibitor0.7321
CYP450 2C9 inhibitorNon-inhibitor0.7022
CYP450 2D6 inhibitorNon-inhibitor0.8516
CYP450 2C19 inhibitorNon-inhibitor0.68
CYP450 3A4 inhibitorNon-inhibitor0.7066
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6339
Ames testNon AMES toxic0.6105
CarcinogenicityCarcinogens 0.529
BiodegradationReady biodegradable0.9077
Rat acute toxicity2.5654 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9094
hERG inhibition (predictor II)Non-inhibitor0.7142
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 cephalosporins. These are compounds containing a 1,2-thiazine fused to a 2-azetidinone to for a oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid moiety or a derivative thereof.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Lactams
Sub Class
Beta lactams
Direct Parent
Cephalosporins
Alternative Parents
N-acyl-alpha amino acids and derivatives / Phenylacetamides / Alkylarylthioethers / 1,3-thiazines / Tetrazoles / Tertiary carboxylic acid amides / Sulfonyls / Alkanesulfonic acids / Heteroaromatic compounds / Organosulfonic acids
show 15 more
Substituents
Cephalosporin / N-acyl-alpha amino acid or derivatives / Alpha-amino acid or derivatives / Phenylacetamide / Aryl thioether / Alkylarylthioether / Meta-thiazine / Monocyclic benzene moiety / Benzenoid / Azole
show 32 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
cephalosporin (CHEBI:3491)

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. Rake JB, Newman DJ, Actor P: Affinity of cefonicid, a long-acting cephalosporin, for the penicillin-binding proteins of Escherichia coli K-12. J Antibiot (Tokyo). 1984 May;37(5):572-6. [PubMed:6376452]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Peptidoglycan glycosyltransferase activity
Specific Function
Essential cell division protein that is required for the synthesis of peptidoglycan at the division septum (PubMed:1103132, PubMed:9614966). Catalyzes the synthesis of cross-linked peptidoglycan fr...
Gene Name
ftsI
Uniprot ID
P0AD68
Uniprot Name
Peptidoglycan synthase FtsI
Molecular Weight
63876.925 Da
References
  1. Rake JB, Newman DJ, Actor P: Affinity of cefonicid, a long-acting cephalosporin, for the penicillin-binding proteins of Escherichia coli K-12. J Antibiot (Tokyo). 1984 May;37(5):572-6. [PubMed:6376452]
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. Rake JB, Newman DJ, Actor P: Affinity of cefonicid, a long-acting cephalosporin, for the penicillin-binding proteins of Escherichia coli K-12. J Antibiot (Tokyo). 1984 May;37(5):572-6. [PubMed:6376452]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Not involved in transpeptidation but exclusively catalyzes a DD-carboxypeptidase and DD-endopeptidase reaction.
Gene Name
dacB
Uniprot ID
P24228
Uniprot Name
D-alanyl-D-alanine carboxypeptidase DacB
Molecular Weight
51797.85 Da
References
  1. Rake JB, Newman DJ, Actor P: Affinity of cefonicid, a long-acting cephalosporin, for the penicillin-binding proteins of Escherichia coli K-12. J Antibiot (Tokyo). 1984 May;37(5):572-6. [PubMed:6376452]
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; PBP-2 is responsible for the determination of the rod shape of the cell. It synthesizes cross-linked peptidoglycan from lipid intermediates.
Gene Name
mrdA
Uniprot ID
P0AD65
Uniprot Name
Penicillin-binding protein 2
Molecular Weight
70856.1 Da
References
  1. Rake JB, Newman DJ, Actor P: Affinity of cefonicid, a long-acting cephalosporin, for the penicillin-binding proteins of Escherichia coli K-12. J Antibiot (Tokyo). 1984 May;37(5):572-6. [PubMed:6376452]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Other/unknown
General Function
Toxic substance binding
Specific Function
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 colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Rodriguez CA, Smith DE: Influence of the unbound concentration of cefonicid on its renal elimination in isolated perfused rat kidneys. Antimicrob Agents Chemother. 1991 Nov;35(11):2395-400. [PubMed:1804013]
  2. Robertson A, Fink S, Karp W: Effect of cephalosporins on bilirubin-albumin binding. J Pediatr. 1988 Feb;112(2):291-4. [PubMed:3339510]
  3. Benson JM, Boudinot FD, Pennell AT, Cunningham FE, DiPiro JT: In vitro protein binding of cefonicid and cefuroxime in adult and neonatal sera. Antimicrob Agents Chemother. 1993 Jun;37(6):1343-7. [PubMed:8328784]

Drug created on June 30, 2007 11:48 / Updated on November 09, 2017 02:58