(4S,4aS,5aS,6S,12aS)-4-(dimethylamino)-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide

• ChemBase ID: 639
• Molecular Formular: C22H24N2O8
• Molecular Mass: 444.43456
• Monoisotopic Mass: 444.15326574
• SMILES: c12c(C(=O)C3=C([C@]4([C@@H](C[C@@H]3[C@@]1(O)C)[C@@H](C(=C(C4=O)C(=O)N)O)N(C)C)O)O)c(ccc2)O
• Canonical SMILES: CN([C@@H]1C(=C(C(=O)N)C(=O)[C@@]2([C@H]1C[C@H]1C(=C2O)C(=O)c2c([C@@]1(C)O)cccc2O)O)O)C
• InChI: InChI=1S/C22H24N2O8/c1-21(31)8-5-4-6-11(25)12(8)16(26)13-9(21)7-10-15(24(2)3)17(27)14(20(23)30)19(29)22(10,32)18(13)28/h4-6,9-10,15,25,27-28,31-32H,7H2,1-3H3,(H2,23,30)/t9-,10-,15-,21+,22-/m0/s1
• InChIKey: OFVLGDICTFRJMM-WESIUVDSSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (4S,4aS,5aS,6S,12aS)-4-(dimethylamino)-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
• IUPAC Traditional name: tetracycline
• Brand Name: Abramycin; Abricycline; Achromycin; Achromycin V; Actisite; Agromicina; Ambramicina; Ambramycin; Amycin; Bio-Tetra; Biocycline; Bristaciclin; Bristaciclina; Bristacycline; Cefracycline; Ciclibion; Copharlan; Criseociclina; Cyclopar; Cytome; Democracin; Deschlorobiomycin; Dumocyclin; Enterocycline; Hostacyclin; Lexacycline; Limecycline; Liquamycin; Medocycline; Mericycline; Micycline; Neocycline; Oletetrin; Omegamycin; Orlycycline; Panmycin; Polycycline; Polyotic; Purocyclina; Resteclin; Retet; Robitet; Roviciclina; SK-Tetracycline; Solvocin; Sumycin; TAC; Tetra-CO; Tetrabon; Tetrachel; Tetracycl; Tetracycline II; Tetracyn; Tetradecin; Tetrafil; Tetramed; Tetraverine; Tetrex; Topicycline; Tsiklomistsin; Tsiklomitsin; Veracin; Vetacyclinum
• Synonyms: Tetracycline HCl; TC; Anhydrotetracycline; Tetracycline; Tetracycline; 四环素

Database IDs

• CAS Number: 60-54-8
• EC Number: 200-481-9
• MDL Number: MFCD00151232
• Beilstein Number: 2230417
• PubChem SID: 46506693; 24888860; 24900120; 160964102
• PubChem CID: 54675776; 5280962

CALCULATED PROPERTIES

JChem

• Acid pKa: -2.2437224
• H Acceptors: 9
• H Donor: 6
• LogD (pH = 5.5): -4.3970165
• LogD (pH = 7.4): -6.222226
• Log P: -3.5476153
• Molar Refractivity: 114.1883 cm^3
• Polarizability: 43.205765 Å^3
• Polar Surface Area: 181.62 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: -0.56
• LOG S: -2.52
• Solubility (Water): 1.33e+00 g/l

PROPERTIES

Physical Property

• Solubility: 231 mg/L at 25 oC (SRC PhysProp experimental -- YALKOWSKY,SH & DANNENFELSER,RM (1992))
• Melting Point: 172-174 °C (dec.)
• Optical Rotation: [α]20/D -230±5°, c = 1% in methanol
• Hydrophobicity(logP): -0.3

Safety Information

• RTECS: QI8750000
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 22
• Safety Statements: 22-36
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H302
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Gloves
• Storage Temperature: -20°C; 2-8°C

Pharmacology Properties

• Gene Information: human ... CYP1A2(1544), TERT(7015)

Product Information

• Purity: ≥88.0% (HPLC); ≥98.0% (NT)
• Suitability: suitable for 1694 per US EPA
• Impurities: 4-11% water
• Empirical Formula (Hill Notation): C22H24N2O8 · xH2O

DETAILS

DrugBank - DB00759

• Drug Groups: approved
• Description: Tetracycline is a broad spectrum polyketide antibiotic produced by the Streptomyces genus of Actinobacteria. It exerts a bacteriostatic effect on bacteria by binding reversible to the bacterial 30S ribosomal subunit and blocking incoming aminoacyl tRNA from binding to the ribosome acceptor site. It also binds to some extent to the bacterial 50S ribosomal subunit and may alter the cytoplasmic membrane causing intracellular components to leak from bacterial cells.
• Indication: Used to treat bacterial infections such as Rocky Mountain spotted fever, typhus fever, tick fevers, Q fever, rickettsialpox and Brill-Zinsser disease. May be used to treat infections caused by Chlamydiae spp., B. burgdorferi (Lyme disease), and upper respiratory infections caused by typical (S. pneumoniae, H. influenzae, and M. catarrhalis) and atypical organisms (C. pneumoniae, M. pneumoniae, L. pneumophila). May also be used to treat acne. Tetracycline may be an alternative drug for people who are allergic to penicillin.
• Pharmacology: Tetracycline is a short-acting antibiotic that inhibits bacterial growth by inhibiting translation. It binds to the 30S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. It also binds to some extent to the 50S ribosomal subunit. This binding is reversible in nature. Additionally tetracycline may alter the cytoplasmic membrane of bacteria causing leakage of intracellular contents, such as nucleotides, from the cell.
• Toxicity: LD₅₀=808mg/kg (orally in mice)
• Affected Organisms: Enteric bacteria and other eubacteria
• Biotransformation: Not metabolized
• Absorption: Bioavailability is less than 40% when administered via intramuscular injection, 100% intravenously, and 60-80% orally (fasting adults). Food and/or milk reduce GI absorption of oral preparations of tetracycline by 50% or more.
• Half Life: 6-12 hours
• Protein Binding: 20 - 67% protein bound
• Elimination: They are concentrated by the liver in the bile and excreted in the urine and feces at high concentrations in a biologically active form.
• References: [Link] ; Griffin MO, Fricovsky E, Ceballos G, Villarreal F: Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol. 2010 Sep;299(3):C539-48. Epub 2010 Jun 30. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Sigma Aldrich - 87128

Other Notes
Review4; Inhibitor of protein synthesis, binds to the 30S subunit and inhibits binding of aminoacyl-tRNAs.
Application
Tetracycline is an inhibitor of protein synthesis and is used in tetracycline controlled gene expression systems (gene switches) such a the tet-on and tet-off systems 1. It is also used to select tetracyline resistant colonies in cell culture 2.
Biochem/physiol Actions
Tetracycline binds to the 30S subunit of the ribosome at the A-site. During protein biosynthesis, the new t-RNA with the amino acid attempts to bind to the A-site of the ribosome. However, since the A-site is blocked by the tetracycline, the aminoacyl-tRNA cannot bind to it. Without the attachment of the tRNA, protein biosynthesis cannot occur. Protein biosynthesis is inhibited and cell death occurs 3.

Sigma Aldrich - T3258

Application
Tetracycline is a broad spectrum polyketide antibiotic. It is used clinically to treat bacterial infections such as Rocky Mountain spotted fever, typhus fever, tick fevers, Q fever, and Brill-Zinsser disease. It is used to treat upper respiratory infections and acne1. It is used to study multidrug resistance2 as well as potential side effects such as acute pancreatitis3.
Biochem/physiol Actions
Tetracycline inhibits bacterial protein synthesis elongation at the level of aminoacyl-tRNA binding to the 30S ribosome. Tetracycline passively diffuses through porin channels in the bacterial cell membrane. It also binds to the bacterial 50S ribosomal subunit which may alter the cytoplasmic membrane, causing intracellular components to leak from bacterial cells1. Mode of resistance is via loss of cell wall permeability.

REFERENCES

• Griffin MO, Fricovsky E, Ceballos G, Villarreal F: Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol. 2010 Sep;299(3):C539-48. Epub 2010 Jun 30. Pubmed
• Link