What is tetracycline?

What is tetracycline?

1. Definition

Tetracycline is an organic compound with the molecular formula C₂₂H₂₄N₂O₈. It and its salts are yellow or light yellow crystals. They are extremely stable in a dry state. Except for chlortetracycline, the aqueous solutions of other tetracyclines are quite stable. Tetracyclines are soluble in dilute acids, alkalis, etc., slightly soluble in water and lower alcohols, but insoluble in ether and petroleum ether.

BALLYA provides a tetracyclines test to tell you if there are tetracyclines residues in dairy products you eat every day.

2. Tetracycline Class

Tetracycline antibiotics mainly include aureomycin, terramycin, doxycycline and tetracycline. Tetracycline antibiotics have a common chemical structure parent. Chlortetracycline and oxytetracycline are both derivatives of tetracycline. The former is chloretracyelin and the latter is oxyeracyein. The tetracycline family are all acid-base amphoteric compounds.

3. Physical and chemical properties

Tetracycline has a molecular formula of C22H24N2O8 and a molecular weight of 444.45. It is a broad-spectrum antibiotic. It is a yellow crystal with bitter taste and melting point 170~175℃ (decomposition). It is slightly soluble in water, soluble in ethanol and acetone, stable in the air, but easy to absorb water, discolor by strong sunlight.

4. What is tetracycline used for?

Tetracycline hydrochloride is a broad-spectrum antibiotic. It has an inhibitory effect on most gram-positive and gram-negative bacteria. The high concentration has a bactericidal effect, and can inhibit rickettsia, trachoma virus, etc., and has a better effect on gram-negative bacilli. Its mechanism of action is mainly to prevent the combination of aminoacyl and ribonucleoprotein bodies, prevent the growth of peptide chains and protein synthesis, thereby inhibiting the growth of bacteria. It also has a bactericidal effect at high concentrations.

There is cross-resistance between tetracycline and oxytetracycline. Clinically, it is mainly used for bacterial dysentery, trachoma, pertussis, pneumonia, purulent meningitis, skin infections, otitis media, etc.

Tetracycline is mainly extracted from the culture broth of Streptomyces viridans or dechlorinated from chlortetracycline. It is not very toxic. But tetracycline acne are common, such as nausea, vomiting, loss of appetite, double infection, affecting bone and tooth growth, etc.

5. History

There have been three generations of tetracycline antibiotics. The first-generation products: chlortetracycline, tetracycline and oxytetracycline are natural antibiotics, which are widely used due to their broad-spectrum, easy-to-use, and economical characteristics.

Later, it was discovered that the chemical structure of these antibiotics was not stable enough, and they were prone to drug resistance. Severe bacterial resistance has led to an urgent need to develop new tetracycline antibiotics. Through extensive structural modification, the second generation semi-synthetic tetracycline antibiotics represented by doxycycline and minocycline were discovered. This kind of antibiotics is more lipophilic and is conducive to cell absorption. However, in recent years, drug-resistant strains have also appeared continuously, which limits its clinical application.

In 2005, the U.S. Food and Drug Administration (FDA) approved the marketing of tigecycline, which has a significant inhibitory effect on the widely drug-resistant Staphylococcus aureus and vancomycin-resistant bacteria. The emergence of glycylcycline antibiotics represented by it marked the birth of the third generation of tetracycline.

Because the necessary pharmacophore for the third-generation tetracycline activity against drug-resistant bacteria is to have a variety of substituents on the D ring, such as glycyl, dimethylamino, fluoro and so on, it is very difficult to construct this kind of structure using previous semi-synthetic methods. It is necessary to develop a new and efficient total synthesis method to construct a D-ring multi-substituted tetracycline skeleton. This also marks the research of tetracycline from semi-synthesis into a new era of total synthesis.

Antibacterial mechanism and resistance mechanism


1. Tetracycline mechanism of action

The antibacterial mechanism of many antibiotics is to interfere with the process of cell division inside or outside the bacteria. Tetracycline antibiotics form a reversible combination with the 30S subunit of the bacterial ribosome to inhibit protein synthesis and have an antibacterial effect. When the antibiotic concentration is low, this reversible competitive binding will also lose its effect, and bacterial protein synthesis will continue.

Tetracycline can also inhibit the synthesis of mitochondrial protein by binding to the mitochondrial 70S subunit. Tetracycline has relatively weak binding ability to the 80S subunit of eukaryotic ribosomes, so the ability to inhibit protein synthesis in eukaryotic cells is also weak. This may be the reason why tetracycline has a strong antibacterial effect but has little side effects on humans.

2. Resistance mechanism

Because tetracycline antibiotics have been widely used for the treatment of bacterial infections in humans and animals for a long time, drug-resistant strains appear in recent years. There are three main mechanisms of drug resistance: active efflux of tetracycline through the efflux pump (such as protein tet A); bacterial ribosome protection (such as protein tet M) to dissociate tetracycline from the 30S subunit; Enzymatic hydrolysis.

Due to the long-term use of tetracycline, tetracycline-resistant bacteria have been found. The resistance of bacteria to tetracyclines is mainly caused by resistance. After the original susceptibility has acquired the resistance gene, the resistant bacteria will be formed, and this resistance gene exists in the plasmid or translocation.

3. Tetracycline resistance gene

Mechanism of action: Tetracycline can bind to a protein of the 30S subunit of the ribosome, thereby inhibiting the translocation process of the ribosome. It encodes a membrane-bound protein composed of 399 amino acids, which prevents tetracycline from entering cells.

Tetracycline side effects

Tetracycline is a representative drug of tetracycline antibiotics, with a broad antibacterial spectrum, and obvious antibacterial effect on most Gram-positive and negative bacteria.

1. Gastrointestinal symptoms

This is one of the common side effects of taking tetracycline tablets. Some patients will experience different degrees of nausea, vomiting, diarrhea, abdominal discomfort and other symptoms after taking tetracycline tablets. It is recommended that you take appropriate physical exercises after taking the medicine and do not stay in bed immediately to reduce the irritation of tetracycline to the gastrointestinal tract.

2. Liver toxicity

Patients taking tetracycline tablets, especially for a long time, have a high probability of fatty liver degeneration and hepatotoxicity, and tetracycline tablets can also cause pancreatitis. I hope everyone will pay attention.

3. Allergy

Taking tetracycline tablets, patients will experience maculopapular rash and erythema, and some patients will experience symptoms of urticaria or allergic purpura, or make the symptoms of the original skin disease worse. And a few patients will have photosensitivity when taking tetracycline. It is recommended that patients take tetracycline tablets to avoid body exposure.

4. Blood System

After taking tetracycline tablets will cause symptoms such as thrombocytopenia and leukopenia, and some patients will have symptoms of hemolytic anemia. It is recommended that related review tests should be done regularly after taking tetracycline tablets.

5. Central Nervous System

After taking tetracycline tablets, some patients will experience increased intracranial pressure such as headaches, vomiting, etc. Patients must stop the drug immediately if these symptoms occur.

6. Nephrotoxicity

Some patients taking tetracycline tablets will have symptoms such as hyperphosphatemia and acidosis, and some patients will experience aggravated original symptoms of kidney disease.

7. Double infection

Long-term use of tetracycline tablets can lead to drug resistance and aggravate infections of the digestive tract, urinary tract, and respiratory tract.

8. Bones

Tetracycline has an effect on the growth and development of bones and teeth, and can also cause tetracycline teeth. Therefore, pregnant women, adolescents and breastfeeding women are prohibited from using this drug.

Detection Methods


The determination methods of tetracycline antibiotics mainly include microbial inhibition method, charmⅡ microbial receptor analysis method, enzyme-linked immunoassay, spectrophotometry, capillary electrophoresis chromatography, thin layer chromatography, high performance liquid chromatography, liquid chromatography-mass spectrometry etc.

After the sample is extracted and purified, the tetracycline antibiotics can be separated by thin layer chromatography or liquid chromatography, and then quantitatively determined by spectrophotometric, fluorescence or mass spectrometry detection systems.

1. Microbiological method

Microbiological method is a traditional analytical method for the determination of tetracyclines and other antibiotics. Microorganisms usually have inherent sensitivity to tetracycline antibiotics. It is particularly sensitive to certain tetracyclines, so the microbial inhibition method is still used. Bacillus cereus ATCC 11778 is a classic microbe used to analyze tetracyclines. Its sensitivity to chlortetracycline is 0.005 mg/L, and 0.025mg/L to tetracycline and oxytetracycline, 0.001~0.002 mg/L to minocycline.

Compared with other analytical methods, the microbial inhibition method is simple to operate, low in price, and does not require sophisticated instruments and complicated sample pretreatment processes, so it is suitable for screening many samples. The biggest disadvantage of the microbial suppression method is that it cannot distinguish the specific types of tetracyclines, so it is difficult to carry out quantitative detection.

2. Indirect enzyme-linked immunosorbent assay

Indirect enzyme-linked immunosorbent assay can be used to detect tetracycline antibiotics in milk. Tetracycline bovine serum albumin conjugate is used for antibody preparation, the homologous tetracycline-casein conjugate is used as the embedding reagent, and goat anti-rabbit IgG-horseradish peroxidase is used as the secondary antibody.

The milk sample was centrifuged to defatted, diluted with a phosphate buffer at a ratio of at least 1:30, and then directly determined by enzyme immunoassay. The detection limit can reach 5 ng/g. Because the antibody used in this method is strongly related to chlortetracycline Therefore, although this method is not used to detect tetracyclines, the detection limit for chlortetracycline is as low as 5 ng/g. Due to the existence of cross-reaction and high false positive rate, immunoassay is generally used as the primary screening method for the detection of tetracyclines.


What is tetracycline? In the early days when tetracycline was created, it was the gospel of mankind. It solved many medically difficult diseases at that time. Antibiotics were abused and developed drug resistance because of this "magic curative effect". And now, how to solve the problem of tetracycline resistance will be a problem for mankind.