What is Tetracycline?

Tetracycline is the most basic compound in the tetracycline family of antibiotics. Both itself and its salts are yellow or pale yellow crystals, which are extremely stable in a dry state. Except for chlortetracycline, other aqueous solutions of the tetracycline family are quite stable. Tetracyclines are soluble in dilute acids and bases, slightly soluble in water and lower alcohols, but insoluble in ether and petroleum ether. Tetracycline antibiotics include chlortetracycline, oxytetracycline, and tetracycline. Tetracycline antibiotics have a common chemical structure parent. Chlortetracycline and oxytetracycline are derivatives of tetracycline. The former is chloretracyelin, and the latter is oxyeracyein. The tetracycline family are both acid-base amphoteric compounds. ^[1]

Tetracycline antibiotics are a class of phenanthrene cores discovered in the 1940s.

There are three generations of tetracycline antibiotics. The first-generation products chlortetracycline, tetracycline, and oxytetracycline are natural antibiotics, which are widely used because of their broad spectrum, ease of use, and economy. ^[7]

The mechanism of antibacterial action of many antibiotics is to interfere with the cell division process inside or outside the bacteria. Tetracycline antibiotics form a reversible conjugate with the 30S subunit of the bacterial inner ribosomes, inhibiting protein synthesis and exerting antibacterial effects. When the antibiotic concentration is low, this reversible competitive binding will also lose effect, and the protein synthesis of bacteria will continue. Tetracycline can also inhibit mitochondrial protein synthesis by binding to the mitochondrial 70S subunit. The ability of tetracycline to bind to the ribosomal 80S subunit of eukaryotic cells is relatively weak, so the ability to inhibit protein synthesis in eukaryotic cells is also weak. This may be the reason for the strong antibacterial effect of tetracycline and the small side effects on humans. ^[7]

Because tetracycline antibiotics have been widely used for a long time to treat bacterial infections in humans and animals, drug-resistant strains have continued to appear in recent years. There are three main types of drug resistance mechanisms: active efflux tetracycline (such as protein tet A) through an efflux pump; bacterial ribosome protection (such as protein tet M) to dissociate tetracycline from the 30S subunit; Enzymatic hydrolysis. ^[7]

Tetracycline antibiotics are usually prepared by biosynthetic and semisynthetic methods. The biosynthesis method is produced by fermentation and extraction under the catalysis of enzymes. Large-scale fermentation production of simple tetracycline drugs still has cost advantages, but it is very difficult to modify the structure of complex tetracycline derivatives. The semi-synthetic method uses biosynthetic antibiotics as raw materials, carries out chemical reactions, and transforms functional groups on the phenanthrane structure to obtain new tetracycline derivatives. Although simple and easy to use, this method has been used for the transformation of tetracycline in the past fifty years. Due to the limited structural changes, the development space for the transformation of tetracyclines has been greatly restricted. ^[7]

Tetracycline antibacterial effect

At present, one of the main drugs for treating periodontitis in clinical practice is tetracycline, minocycline and doxycycline. The above three drugs have strong antibacterial effects, but the antibacterial activity of minocycline and doxycycline Higher than tetracycline, and less resistant to bacteria. These drugs have the characteristics of long half-life (about 20h) and high drug concentration, but the latter two have higher drug concentrations than plasma. Some scholars have shown that the use of tetracyclines to treat various periodontitis-related suspected bacteria has a strong antibacterial effect, especially for P. gingivalis and Actinomycetes; at the same time, it can adhere to the surface of tooth root , Not easily washed away by gingival crevicular fluid, and then maintain antibacterial activity for a long time. Some scholars have shown that the application of minocycline treatment in periodontitis can significantly exert antibacterial spectrum efficacy based on bacteriostatic effect, and it is clinically used as a first-line drug for periodontitis. ^[8]

Tetracycline Regulates Host Action

Tetracycline drugs not only have bacteriostatic effects, but also have the ability to regulate the host body, and the main response of the host body lies in the non-bacterial properties of the tetracycline drugs. ^[8]

Tetracycline inhibits collagenase

Collagenase is mainly derived from neutrophils and cells. It is a matrix metalloproteinase, which can be divided into two types, namely recessive and active. The latter requires the participation of metal cations, which in turn plays a role in degrading collagen fibers. At the same time, it can destroy periodontal connective tissue and further increase alveolar bone absorption, leading to worsening periodontal inflammation. Tetracyclines It can be combined with metal cations possessed by collagenase, so as to inhibit the production and secretion of collagenase. In addition, it can also reduce collagenase activity in gingival crevicular fluid, which is beneficial to relieve clinical symptoms. ^[8]

Tetracycline bone tissue cells and periodontal tissue cells

Some scholars have shown that tetracycline drugs can inhibit bone tissue dissolution and absorption, mainly by inhibiting the activity of MMPs, and then play a role in destroying the structure and function of bone tissue. If tetracycline drugs are used in sub-dose, they can further promote fiber Cell differentiation and proliferation, thereby destroying the regeneration and reconstruction of periodontal tissue. ^[8]