Identification

Name
Chlortetracycline
Accession Number
DB09093
Type
Small Molecule
Groups
Approved, Investigational, Vet approved
Description

Chlortetracycline is a tetracycline antibiotic, the first tetracycline to be identified. It was discovered in 1945 by Benjamin Minge Duggar working at Lederle Laboratories under the supervision of Yellapragada Subbarow. Duggar identified the antibiotic as the product of an actinomycete he cultured from a soil sample collected from Sanborn Field at the University of Missouri. The organism was named Streptomyces aureofaciens and the isolated drug, Aureomycin, because of their golden color.

Structure
Thumb
Synonyms
Not Available
Product Ingredients
IngredientUNIICASInChI Key
Chlortetracycline bisulfate1D06KZ672I27823-62-7GQUMQTDURIYYIA-MRFRVZCGSA-N
Chlortetracycline calcium complexNR4B2SX17S57122-99-3BRXWPGYMDYZZNU-NAUDNZITSA-L
Chlortetracycline hydrochlorideO1GX33ON8R64-72-2CBHYYLPALVVVEY-MRFRVZCGSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Aureomycin - Ont Top 3%Ointment3 %TopicalWyeth Ayerst Canada Inc.1997-10-242000-08-02Canada
Aureomycin Ont 3%Ointment3 %TopicalLederle Cyanamid Canada Inc.1952-12-311997-11-24Canada
Aureomycin Ont Oph 1%Ointment1 %OphthalmicLederle Cyanamid Canada Inc.1955-12-311997-01-14Canada
Categories
UNII
WCK1KIQ23Q
CAS number
57-62-5
Weight
Average: 478.88
Monoisotopic: 478.114293429
Chemical Formula
C22H23ClN2O8
InChI Key
CYDMQBQPVICBEU-XRNKAMNCSA-N
InChI
InChI=1S/C22H23ClN2O8/c1-21(32)7-6-8-15(25(2)3)17(28)13(20(24)31)19(30)22(8,33)18(29)11(7)16(27)12-10(26)5-4-9(23)14(12)21/h4-5,7-8,15,26,28-29,32-33H,6H2,1-3H3,(H2,24,31)/t7-,8-,15-,21-,22-/m0/s1
IUPAC Name
(4S,4aS,5aS,6S,12aS)-7-chloro-4-(dimethylamino)-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboximidic acid
SMILES
[H][C@]12C[C@@]3([H])[C@]([H])(N(C)C)C(O)=C(C(O)=N)C(=O)[C@@]3(O)C(O)=C1C(=O)C1=C(O)C=CC(Cl)=C1[C@@]2(C)O

Pharmacology

Indication

Used in the manufacuring of medicated animal feeds [Label].

Pharmacodynamics

Tetracycline antibiotics are bacteriostatic agents which act to inhibit bacterial growth and reproduction [2].

Mechanism of action

Chlortetracycline, like other tetracyclines, competes for the A site of the bacterial ribosome [2]. This binding competes with tRNA carrying amino acids preventing the addition of more amino acids to the peptide chain. This inhibition of protein synthesis ultimately inhibits growth and reproduction of the bacterial cell as necessary proteins cannot be synthesized.

TargetActionsOrganism
A16S rRNA
inhibitor
Enteric bacteria and other eubacteria
A30S ribosomal protein S3
inhibitor
Escherichia coli (strain K12)
A30S ribosomal protein S8
inhibitor
Escherichia coli (strain K12)
A30S ribosomal protein S19
inhibitor
Escherichia coli (strain K12)
A30S ribosomal protein S14
inhibitor
Escherichia coli (strain K12)
A30S ribosomal protein S7
inhibitor
Escherichia coli (strain K12)
Absorption

Chortetracycline reaches peak plasma concentation in about 3 hours [1]. Its oral bioavailability is 25-30%.

Volume of distribution

Chlortetracycline has a volume of distribution of 100 liters [1].

Protein binding

Chlortetracline is 50-55% bound to plasma proteins [1].

Metabolism

Chlortetracycline is not known to undergo significant metabolism [1].

Route of elimination

Chlortetracycline is mainly eliminated in feces [1]. Renal function does not appear to affect the rate of elimination.

Half life

The half-life of Chlortetracycline is 5.6 hours [1].

Clearance
Not Available
Toxicity

The acute oral LD50 in mice is 2314mg/kg [MSDS].The most common adverse effects of tertacylines are gastrointestinal disturbances, and staining of teeth and bone. Some occurences of dental hypoplasia and bone deformity have been noted [2]. In pregnant women tetracyclines may produce hepatotoxicity.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Agwuh KN, MacGowan A: Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines. J Antimicrob Chemother. 2006 Aug;58(2):256-65. Epub 2006 Jul 1. [PubMed:16816396]
  2. 49, 50. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 614, 629). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
External Links
KEGG Compound
C06571
PubChem Compound
54708735
PubChem Substance
310265020
ChemSpider
10469370
ChEBI
27644
ChEMBL
CHEMBL404520
HET
CTC
Wikipedia
Chlortetracycline
ATC Codes
S01AA02 — ChlortetracyclineJ01AA03 — ChlortetracyclineJ01AA20 — Combinations of tetracyclinesA01AB21 — ChlortetracyclineD06AA02 — Chlortetracycline
PDB Entries
2fj1 / 2tct / 2y6r / 3egz / 4v2g / 5tui
FDA label
Download (218 KB)
MSDS
Download (179 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
OintmentTopical3 %
OintmentOphthalmic1 %
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)Decomposes at 210-215MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.288 mg/mLALOGPS
logP0.11ALOGPS
logP-2.9ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)3.58ChemAxon
pKa (Strongest Basic)7.97ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area182.61 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity129.93 m3·mol-1ChemAxon
Polarizability45.69 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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 tetracyclines. These are polyketides having an octahydrotetracene-2-carboxamide skeleton, substituted with many hydroxy and other groups.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Tetracyclines
Sub Class
Not Available
Direct Parent
Tetracyclines
Alternative Parents
Naphthacenes / Anthracenecarboxylic acids and derivatives / Tetralins / Aryl ketones / 1-hydroxy-2-unsubstituted benzenoids / Aralkylamines / Cyclohexenones / Aryl chlorides / Vinylogous acids / Tertiary alcohols
show 9 more
Substituents
Tetracycline / Tetracene / Naphthacene / Anthracene carboxylic acid or derivatives / Tetralin / Aryl ketone / 1-hydroxy-2-unsubstituted benzenoid / Cyclohexenone / Aralkylamine / Aryl chloride
show 26 more
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
tertiary alcohol, tertiary amino compound, monocarboxylic acid amide, monochlorobenzenes, tetracyclines (CHEBI:27644) / Linear tetracyclines (C06571) / Linear tetracyclines (LMPK07000004)

Targets

1. 16S rRNA
Kind
Nucleotide
Organism
Enteric bacteria and other eubacteria
Pharmacological action
Yes
Actions
Inhibitor
References
  1. Nawaz M, Sung K, Khan SA, Khan AA, Steele R: Biochemical and molecular characterization of tetracycline-resistant Aeromonas veronii isolates from catfish. Appl Environ Microbiol. 2006 Oct;72(10):6461-6. [PubMed:17021193]
  2. Domingue GJ Sr: Cryptic bacterial infection in chronic prostatitis: diagnostic and therapeutic implications. Curr Opin Urol. 1998 Jan;8(1):45-9. [PubMed:17035842]
  3. Pringle M, Fellstrom C, Johansson KE: Decreased susceptibility to doxycycline associated with a 16S rRNA gene mutation in Brachyspira hyodysenteriae. Vet Microbiol. 2007 Jul 20;123(1-3):245-8. Epub 2007 Feb 25. [PubMed:17428623]
  4. Rasmussen B, Noller HF, Daubresse G, Oliva B, Misulovin Z, Rothstein DM, Ellestad GA, Gluzman Y, Tally FP, Chopra I: Molecular basis of tetracycline action: identification of analogs whose primary target is not the bacterial ribosome. Antimicrob Agents Chemother. 1991 Nov;35(11):2306-11. [PubMed:1725100]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Structural constituent of ribosome
Specific Function
Binds the lower part of the 30S subunit head. Binds mRNA in the 70S ribosome, positioning it for translation (By similarity).Plays a role in mRNA unwinding by the ribosome, possibly by forming part...
Gene Name
rpsC
Uniprot ID
P0A7V3
Uniprot Name
30S ribosomal protein S3
Molecular Weight
25983.07 Da
References
  1. Buck MA, Cooperman BS: Single protein omission reconstitution studies of tetracycline binding to the 30S subunit of Escherichia coli ribosomes. Biochemistry. 1990 Jun 5;29(22):5374-9. [PubMed:2200507]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Structural constituent of ribosome
Specific Function
One of the primary rRNA binding proteins, it binds directly to 16S rRNA central domain where it helps coordinate assembly of the platform of the 30S subunit.Protein S8 is a translational repressor ...
Gene Name
rpsH
Uniprot ID
P0A7W7
Uniprot Name
30S ribosomal protein S8
Molecular Weight
14126.435 Da
References
  1. Buck MA, Cooperman BS: Single protein omission reconstitution studies of tetracycline binding to the 30S subunit of Escherichia coli ribosomes. Biochemistry. 1990 Jun 5;29(22):5374-9. [PubMed:2200507]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Trna binding
Specific Function
In the E.coli 70S ribosome in the initiation state (PubMed:12809609) it has been modeled to contact the 23S rRNA of the 50S subunit forming part of bridge B1a; this bridge is broken in the model wi...
Gene Name
rpsS
Uniprot ID
P0A7U3
Uniprot Name
30S ribosomal protein S19
Molecular Weight
10430.235 Da
References
  1. Buck MA, Cooperman BS: Single protein omission reconstitution studies of tetracycline binding to the 30S subunit of Escherichia coli ribosomes. Biochemistry. 1990 Jun 5;29(22):5374-9. [PubMed:2200507]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Structural constituent of ribosome
Specific Function
Binds 16S rRNA, required for the assembly of 30S particles and may also be responsible for determining the conformation of the 16S rRNA at the A site.
Gene Name
rpsN
Uniprot ID
P0AG59
Uniprot Name
30S ribosomal protein S14
Molecular Weight
11580.36 Da
References
  1. Buck MA, Cooperman BS: Single protein omission reconstitution studies of tetracycline binding to the 30S subunit of Escherichia coli ribosomes. Biochemistry. 1990 Jun 5;29(22):5374-9. [PubMed:2200507]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Trna binding
Specific Function
One of the primary rRNA binding proteins, it binds directly to 16S rRNA where it nucleates assembly of the head domain of the 30S subunit. Is located at the subunit interface close to the decoding ...
Gene Name
rpsG
Uniprot ID
P02359
Uniprot Name
30S ribosomal protein S7
Molecular Weight
20018.91 Da
References
  1. Buck MA, Cooperman BS: Single protein omission reconstitution studies of tetracycline binding to the 30S subunit of Escherichia coli ribosomes. Biochemistry. 1990 Jun 5;29(22):5374-9. [PubMed:2200507]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
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. Bratlid D, Bergan T: Displacement of albumin-bound antimicrobial agents by bilirubin. Pharmacology. 1976;14(5):464-72. [PubMed:1031216]

Drug created on September 16, 2015 11:03 / Updated on October 01, 2018 16:41