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Tetracycline (NSC-108579, Sumycin among others) is a potent and broad-spectrum antibiotic used to treat a number of infections such as gram-positive and gram-negative bacteria. This includes acne, cholera, brucellosis, plague, malaria, and syphilis. It possesses some level of bacteriostatic activity against almost all medically relevant aerobic and anaerobic bacterial genera, both Gram-positive and Gram-negative.
Physicochemical Properties
| Molecular Formula | C22H4N2O8 |
| Molecular Weight | 444.4346 |
| Exact Mass | 444.153 |
| Elemental Analysis | C, 59.46; H, 5.44; N, 6.30; O, 28.80 |
| CAS # | 60-54-8 |
| Related CAS # | Tetracycline-d6;2373374-42-4;Tetracycline hydrochloride;64-75-5 |
| PubChem CID | 54675776 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.3809 |
| Boiling Point | 554.44°C |
| Melting Point | 175-177 °C(lit.) |
| Flash Point | 432.0±32.9 °C |
| Vapour Pressure | 0.0±2.9 mmHg at 25°C |
| Index of Refraction | 1.6500 |
| LogP | -1.47 |
| Hydrogen Bond Donor Count | 6 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 32 |
| Complexity | 971 |
| Defined Atom Stereocenter Count | 5 |
| SMILES | O([H])[C@@]12C(=C(C(N([H])[H])=O)C([C@]([H])([C@]1([H])C([H])([H])[C@@]1([H])C(=C(C3C(=C([H])C([H])=C([H])C=3[C@@]1(C([H])([H])[H])O[H])O[H])O[H])C2=O)N(C([H])([H])[H])C([H])([H])[H])=O)O[H] |
| InChi Key | OFVLGDICTFRJMM-WESIUVDSSA-N |
| InChi Code | 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 |
| Chemical Name | 2-Naphthacenecarboxamide, 4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-, (4S,4aS,5aS,6S,12aS)- |
| Synonyms | Mericycline; Micycline; Neocycline; NSC 108579; NSC-108579; NSC108579 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product is not stable in solution, please use freshly prepared working solution for optimal results. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Tetracycline |
| ln Vitro |
With a MIC value of 0.5 g/mL, tetracycline demonstrates susceptibility to V. vulnificus strain B3547[2]. Tetracycline breaks down pre-formed fibrils and prevents the formation of L-amyloid aggregates[3]. |
| ln Vivo | Mice with bacteremia are rescued from death by tetracycline (3 mg/kg; i.p. every 12 h until survive)[2]. |
| Animal Protocol | Animal Model: 30 to 40 g female V. vulnificus strain B3547 infected ICR mice[2] Dosage: 3 mg/kg Administration: Intraperitoneal injection; 3 mg/kg every 12h until survive Result: prevented human CNE-2 xenografts from growing in nude mice. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion 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. They are concentrated by the liver in the bile and excreted in the urine and feces at high concentrations in a biologically active form. ALL TETRACYCLINES ARE ADEQUATELY BUT INCOMPLETELY ABSORBED FROM GI TRACT. MOST ABSORPTION TAKES PLACE FROM STOMACH & UPPER SMALL INTESTINE & IS GREATEST IN FASTING STATE. /TETRACYCLINES/ ... /TETRACYCLINE IS/ VERY INCOMPLETELY ABSORBED. AFTER SINGLE ORAL DOSE PEAK PLASMA CONCN ARE ATTAINED IN 2-4 HR. ... ADMIN OF 250 MG EVERY 6 HR PRODUCES PEAK PLASMA CONCN OF APPROX 2-2.5 UG/ML. THE PRIMARY ROUTE OF ELIMINATION FOR MOST TETRACYCLINES IS THE KIDNEY, ALTHOUGH THEY ARE ALSO CONCENTRATED IN THE LIVER AND EXCRETED BY ... BILE, INTO INTESTINE, FROM WHICH THEY ARE PARTIALLY REABSORBED. /TETRACYCLINES/ ELIMINATION FROM INTESTINAL TRACT OCCURS EVEN WHEN DRUGS ARE GIVEN PARENTERALLY, AS RESULT OF EXCRETION IN BILE. /TETRACYCLINES/ For more Absorption, Distribution and Excretion (Complete) data for TETRACYCLINE (16 total), please visit the HSDB record page. Metabolism / Metabolites Not metabolized Biological Half-Life 6-12 hours /IT HAS HALF-LIFE/ IN RANGE OF 6-12 HR... Tetracycline was encapsulated in erythrocytes by a dialysis technique. On encapsulation of (14)C sucrose and (3)H tetracycline, the drug concn (0.2 mg/ml of erythrocytes) decreased the tetracycline encapsulation, but not (14)C sucrose. Carrier erythrocytes containing tetracycline reinjected in calves were studied for their pharmacokinetic constants. the drug half-life was 6.7 hr with an overall elimination constant of 0.104 hr. The serum half-life...is 6-12 hr in adults with normal renal funtion and is reported to be 57-120 hr in patients with severe renal impairment. |
| Toxicity/Toxicokinetics |
Interactions TETRACYCLINE ITSELF HAS BEEN SHOWN TO HAVE DIRECT, PH-DEPENDENT EFFECT ON RAT INTESTINE, RESULTING IN INCR ABSORPTION OF SULFANILIC ACID. ORAL ADMIN OF FERROUS SULFATE (200-600 MG) INTERFERES WITH ABSORPTION OF TETRACYCLINE FROM GI TRACT & VICE VERSA, LEADING TO DECR SERUM LEVELS OF ANTIBIOTIC & IRON SALT, RESPECTIVELY. ... OTHER SALTS OF IRON SUCH AS FERROUS FUMARATE & FERROUS GLUCONATE HAVE BEEN SHOWN TO INTERACT WITH TETRACYCLINE. BILIARY EXCRETION OF TETRACYCLINE ... IS INCR IN RATS BY TWO NEW CHOLERETIC AGENTS ALPHA,ALPHA-DIETHYL-1-NAPHTHYLACETIC ACID (DA 808) & ALPHA-METHYL-ALPHA-(2-MORPHOLINOETHYL)-1-NAPHTHYLACETIC ACID (DA 1627). ... AS DA 808 & DA 1627 CAUSE NO DECR IN TETRACYCLINE ... CONCN IN BILE, THEY APPEAR TO ACT AS TRUE CHOLERETICS. ... ABSORPTION OF THESE AGENTS IS IMPAIRED BY CONCURRENT INGESTION OF DAIRY PRODUCTS; ALUMINUM HYDROXIDE GELS; CALCIUM, MAGNESIUM, & IRON OR ZINC SALTS; AND BISMUTH SUBSALICYLATE . MECHANISMS RESPONSIBLE FOR DECR ABSORPTION APPEAR TO BE CHELATION OF DIVALENT AND TRIVALENT CATIONS. /TETRACYCLINES/ For more Interactions (Complete) data for TETRACYCLINE (22 total), please visit the HSDB record page. Non-Human Toxicity Values LD50 Rat oral 807 mg/kg LD50 Mouse oral 678 mg/kg LD50 Guinea pig oral 1875 mg/kg |
| References |
[1]. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology ofbacterial resistance. Microbiol Mol Biol Rev. 2001 Jun;65(2):232-60. [2]. Antibiotic efficacy against Vibrio vulnificus in the mouse: superiority of tetracycline. J Pharmacol Exp Ther. 1983 Jun;225(3):595-8. [3]. Anti-amyloidogenic activity of tetracyclines: studies in vitro. FEBS Lett. 2001 Jan 5;487(3):404-7. |
| Additional Infomation |
Tetracycline (internal use) can cause developmental toxicity according to state or federal government labeling requirements. Tetracycline is a broad-spectrum polyketide antibiotic produced by the Streptomyces genus of actinobacteria. It has a role as an antimicrobial agent, an antibacterial drug, an antiprotozoal drug, a protein synthesis inhibitor and an Escherichia coli metabolite. It is a tertiary alpha-hydroxy ketone and a member of tetracyclines. It is a conjugate acid of a tetracycline(1-) and a tetracycline zwitterion. 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. The FDA withdrew its approval for the use of all liquid oral drug products formulated for pediatric use containing tetracycline in a concentration greater than 25 mg/ml. Other formulations of tetracycline continue to be used. Tetracycline is a Tetracycline-class Antimicrobial. Tetracycline is a broad-spectrum naphthacene antibiotic produced semisynthetically from chlortetracycline, an antibiotic isolated from the bacterium Streptomyces aureofaciens. In bacteria, tetracycline binds to the 30S ribosomal subunit, interferes with the binding of aminoacyl-tRNA to the mRNA-ribosome complex, thereby inhibiting protein synthesis. A naphthacene antibiotic that inhibits AMINO ACYL TRNA binding during protein synthesis. See also: Tetracycline Hydrochloride (has salt form); Tetracycline Phosphate Complex (is active moiety of); Tetracycline Phosphate (is active moiety of) ... View More ... Drug 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. Mechanism of Action Tetracycline passively diffuses through porin channels in the bacterial membrane and reversibly binds to the 30S ribosomal subunit, preventing binding of tRNA to the mRNA-ribosome complex, and thus interfering with protein synthesis. TETRACYCLINES ARE THOUGHT TO INHIBIT PROTEIN SYNTH BY BINDING SPECIFICALLY TO 30 S RIBOSOMES AND PREVENTING ACCESS OF AMINOACYL TRNA TO... MRNA-RIBOSOME COMPLEX. /TETRACYCLINES/ ... IT IS POSSIBLE THAT REVERSIBLY BOUND ANTIBIOTIC IS RESPONSIBLE FOR ANTIBACTERIAL ACTION. /TETRACYCLINES/ TETRACYCLINE COMBINES WITH CELLULAR & INTRACELLULAR MATERIAL TO FORM A FLUOROPHORE WHICH UNDER UV LIGHT GLOWS WITH YELLOW-GOLD FLUORESCENCE. THE FLUOROPHORE REMAINS IN BONE FOR MANY MO. PHOTOALLERGIC REACTIONS ARE BELIEVED TO RESULT FROM LIGHT ENERGY ACTING ON OR ALTERING DRUG & SKIN PROTEINS IN SUCH MANNER AS TO FORM AN ANTIGEN. THESE ERUPTIONS REQUIRE PREVIOUS CONTACT WITH OFFENDING SUBSTANCE, ARE NOT DOSE-RELATED, & EXHIBIT CROSS-SENSITIVITY WITH CHEM RELATED COMPD. /TETRACYCLINES/ For more Mechanism of Action (Complete) data for TETRACYCLINE (6 total), please visit the HSDB record page. Therapeutic Uses Antibiotics, Tetracycline; Protein Synthesis Inhibitors Tetracycline hydrochloride ointment is used in the prophylaxis of minor bacterial skin infections and in the treatment of dermal ulcer. /Tetracycline hydrochloride; NOT included in US product labeling/ Tetracycline hydrochloride ointment is indicated in the topical treatment of minor skin infections caused by streptococci, staphylococci, and other susceptible organisms. /Tetracycline hydrochloride; Included in US product labeling/ Tetracycline hydrochloride for topical solution is indicated for the topical treatment of acne vulgaris. It may be effective in grades II and III acne, which are characterized by inflammatory lesions such as papules and pustules. /Tetracycline hydrochloride; Included in US product labeling/ For more Therapeutic Uses (Complete) data for TETRACYCLINE (37 total), please visit the HSDB record page. Drug Warnings EXCEPT FOR LOCAL USE IN EYE, TOPICAL USE OF TETRACYCLINES IS NOT RECOMMENDED. /TETRACYCLINES/ MICROORGANISMS THAT HAVE BECOME INSENSITIVE TO ONE TETRACYCLINE FREQUENTLY EXHIBIT RESISTANCE TO OTHERS. /TETRACYCLINES/ CROSS-SENSITIZATION AMONG VARIOUS TETRACYCLINES IS COMMON . /TETRACYCLINES/ ... NAUSEA, VOMITING, POLYURIA, POLYDIPSIA, PROTEINURIA, ACIDOSIS, GLYCOSURIA, & GROSS AMINOACIDURIA, A FORM OF FANCONI SYNDROME, HAS BEEN OBSERVED IN PT INGESTING OUTDATED, & DEGRADED TETRACYCLINE. For more Drug Warnings (Complete) data for TETRACYCLINE (31 total), please visit the HSDB record page. Pharmacodynamics 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. |
Solubility Data
| Solubility (In Vitro) |
DMSO : 89~125 mg/mL (200.25~281.26 mM) Ethanol : ~22 mg/mL H2O : < 0.1 mg/mL |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.68 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.68 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2501 mL | 11.2504 mL | 22.5007 mL | |
| 5 mM | 0.4500 mL | 2.2501 mL | 4.5001 mL | |
| 10 mM | 0.2250 mL | 1.1250 mL | 2.2501 mL |