Хлортетрациклин

Описание

Chlortetracycline (Brand name: Aureomycin) is the 7-chloro substitution derivative of the tetracycline and has a golden color. As a veterinary medicine, chlortetracycline is commonly used for the treatment of conjunctivitis of cats. It can also be used in the treatment of infections occurring in the urinary tract, respiratory tract, and the intestines. Its mechanism of action is through inhibiting the protein synthesis, inhibiting the binding of aminoacyl-tRNA to the mRNA-ribosome complex through binding to the 30S ribosome subunit.

Химические свойства

Golden-yellow crystalline powder, odorless with a bitter taste; decomposes at a melting point of 168-169°C. Slightly soluble in water but soluble in saline solutions. The hydrochloride form is slightly soluble in methanol, water, and ethanol and insoluble in acetone, ether, and chloroform. Stable in air, but the colour gradually darkens upon exposure to light.

Использование

Chlortetracycline was the first reported member of the tetracycline class, isolated from Streptomyces aureofaciens in 1948. Chlortetracyclines heralded the early wave of antibiotic discoveries from microbes and after 50 years are still widely used as pharmaceuticals. Chlortetracycline is a pigment and, like most pigments, is extremely sensitive to environmental and storage conditions. Commercial chlortetracycline may contain significant levels of degradation products.

Показания

Chlorotetracycline, an antibiotic with a broad spectrum of action, causes a bacteriostatic effect with respect to Gram-positive (staphylococci, including those that produce penicillinase; streptococci, pneumococci; clostridia, listeria, and anthrax bacillus) and Gram-negative microorganisms (gonococci, whooping cough bacillus, colon bacillus, enterobacteria, klebisella, salmonella, shigella), as well as Rickettsia, chlamydia, mycoplasma, and spirochaeta. Blue-pus bacillus, proteus, serracia, most strains of Bacteroides fragilis, most fungi, and small viruses are resistant to this drug. It is used for pneumonia, bronchitis, empyema of the lungs, angina, cholecystitis, whooping cough, endocarditis, endometritis, intestinal infections, prostatitis, syphilis, gonorrhea, brucellosis, osteomyelitis, purulent infections of soft tissues, and others caused by microorganisms sensitive to this drug. Synonyms of this drug are aureomycin, biomycin, xanthomycin, and others.

Определение

ChEBI: Chlortetracycline is a member of the class of tetracyclines with formula C22H23ClN2O8 isolated from Streptomyces aureofaciens. It has a role as an antiprotozoal drug, a fluorescent probe, a calcium ionophore and an antibacterial drug. It is a member of monochlorobenzenes, a tertiary amino compound, a tertiary alcohol, a monocarboxylic acid amide, a tertiary alpha-hydroxy ketone and a member of tetracyclines. It is a conjugate acid of a chlortetracycline(1-).

Антимикробная активность

It is slightly less active than tetracycline against many bacteria, with the exception of Gram-positive organisms.

Фармацевтические приложения

7-Chlortetracycline. A fermentation product of certain strains of Streptomyces aureofaciens. Formulated as the hydrochloride or the free base for oral or topical application.

Фармакокине?тика

Oral absorption：30–60%
C_max 500 mg oral：2.5–7 mg/L：
Plasma half-life： 5–6 h
Volume of distribution： c.2 L/kg
Plasma protein binding： 47–65%
Absorption is relatively poor compared with other tetracyclines. It undergoes rapid metabolism and is largely eliminated by biliary excretion, with only a small proportion eliminated via the kidney. Despite this, chlortetracycline is not recommended for patients in renal failure, since accumulation occurs as a consequence of the half-life increase to approximately 7–11 h.

Клиническое использование

Its uses are those common to the group. It has also been used topically in the management of recurrent aphthous ulcers of the mouth, but experience is limited and the mechanism of action is unknown.

Побочные эффекты

Side effects are typical of the group. Contact hypersensitivity has been reported with topical application to abraded skin and varicose ulcers.

Профиль безопасности

Poison by intravenous and intraperitoneal routes. Moderately toxic by ingestion. Experimental reproductive effects. When heated to decomposition it emits toxic fumes of Cland NOx. See also TETRACYCLINE.

Методы очистки

Aureomycin is dehydrated by azeotropic distillation of its solution with toluene. On cooling, the anhydrous material crystallises out and is recrystallised from *C6H6, then dried under vacuum at 100o over paraffin wax. (If it is crystallised from MeOH, it contains MeOH which is not removed on drying.) [Stephens et al. J Am Chem Soc 76 3568 1954, Laskin & Chan Biochem Biophys Res Commun 14 137 1964]. [Beilstein 14 IV 2631.]