Tetracycline group

Doxycycline (Vibramycin) is an antibiotic belonging to die tetracycline group of antibiotics. The adverse reactions associated with this drug are discussed in Chapter 9 and include photosensitivity, anorexia, nausea, and vomiting. 

Many natural aromatic compounds are produced from the cyclization of poly- -keto chains by enzymic aldol and Claisen reactions. Examples include simple structures like orsellinic acid and phloracetophenone, and more complex highly modified structures of medicinal interest, such as mycophenolic acid, used as an immunosuppressant drug, the antifungal agent griseofulvin, and antibiotics of the tetracycline group, e.g. tetracycline itself. 

The same test kit has been also applied to detect all members of the tetracycline group of antibiotics in kidney and meat tissue (72), although its crossreactivity varied from 4-5% for oxytetracycline and doxycycline to 100% for tetracycline and chlortetracycline. However, the applied sample preparation procedure... 

European Community Commission Regulation No. 2701/94 (21) states that the maximum residue level (MRL) for all substances belonging to the tetracycline group is the sum of the residues of all substances within the group. This legislative requirement necessitates the development and use of analytical methods capable of simultaneously detecting residues of more than one tetracycline. The MRLs for combined tetracycline residues are 600 yug/kg, 100 /U,g/kg, and 100 /u,g/kg in kidney, muscle, and milk, respectively (22). 

Alteration of the tetracycline molecule (7) is not normally considered as being a mechanism of bacterial insusceptibility to the tetracycline group of antibiotics [192, 193]. Nevertheless, there have been recent examples of tetracycline modification, ostensibly associated with the tetB determinant [194, 195],... 

Pomserantsev, A.P., Shishkova, N.A., Marinin, L.I. (1992). Comparison of therapeutic effects of antibiotics of the tetracycline group in the treatment of anthrax caused by a strain inheriting tet- gene of plasmid pBC16. Antibiot. Khimioter. 37 31-4. (In Russian)... 

Doxycydine, USP. A more recent addition to tlie tetracycline group of antibiotics available for antibuclcrial therapy is doxycydine. o-6-dcoxy-5-oxytctracyclinc (Vibra-mycin). first reported by Stephens et al. " in 1958. It was obtained first in small yields by a chemical transformation of oxytetracycline. but it is now pnxluccd by catalytic hydrogenation of methacyclinc or by reduction of a bcn/ylmcreap-tan derivative of methacyclinc with Raney nickel. The latter... 

Ishiie, T., Doi, Y., Yora, K. and Asuyama H. (1967). Suppressive effects of antibiotics of tetracycline group on symptom development of mulberry dwarf disease. Annals of Phytopathological Society of Japan, 33 267-275. 

Investigation of the metabolic effects of fusidic acid in man [334] have shown that, like the tetracycline group, it has a mild catabolic effect upon protein metabolism. It also shows a hypocalciuric effect and a moderate reduc-tion in bromsulphthalein excretion, with the latter probably arising from a competition between the metabolites of fusidic acid and the bromsulphthalein for a common transport mechanism involved in the excretion into the bile. Seven such metabohtes of fusidic acid have been isolated from human bile [335]. 

Colicin Ea Streptogramin B Fusidic acid Tetracycline group ... 

M.p. 296 C. Accepts an electron from suitable donors forming a radical anion. Used for colorimetric determination of free radical precursors, replacement of Mn02 in aluminium solid electrolytic capacitors, construction of heat-sensitive resistors and ion-specific electrodes and for inducing radical polymerizations. The charge transfer complexes it forms with certain donors behave electrically like metals with anisotropic conductivity. Like tetracyanoethylene it belongs to a class of compounds called rr-acids. tetracyclines An important group of antibiotics isolated from Streptomyces spp., having structures based on a naphthacene skeleton. Tetracycline, the parent compound, has the structure ... 

The 7-chloro-derivative, the first of the group to be isolated (1948) is known as chlortetracy-cline. The 5-hydroxy-derivative is oxytetracy-dine. More recently introduced tetracyclines are 6-demethyl-7-chlorotetracycline and 5-hydroxy-6-deoxy-6-methyienetetracycline. 

Tetracyclines. The tetracycliaes are a small group of antibiotics characterized as containing a polyhydronaphthacene nucleus. Commercially the tetracyclines are very important. They have been used clinically against gram-positive and gram-negative bacteria, spirochete, mycoplasmas, and rickettsiae... 

The tetracyclines are a group of antibiotics having an identical 4-ring carbocycHc structure as a basic skeleton and differing from each other chemically only by substituent variation. Figure 1 shows the principal tetracycline derivatives now used commercially. 

The tetracycline molecule (1) presents a special challenge with regard to the study of stmcture—activity relationships. The difficulty has been to devise chemical pathways that preserve the BCD ring chromophore and its antibacterial properties. The labiUty of the 6-hydroxy group to acid and base degradation (12,13), plus the ease of epimerization (23) at position 4, contribute to chemical instabiUty under many reaction conditions. 

Reactions at the C-5 position of the tetracycline molecule have been limited to the iatroduction of an alkoxy group (42) and the acetylation of the hydroxyl group (43) ia 5-hydroxytetracycline. Neither of these modifications improved the biological activity of the molecule. 

In the United States, the manufacturers of fermentation-derived tetracyclines (1), (2), and (3) are the Ledede Laboratories, a division of American Cyanamid Co., Charles Pfizer Inc., Bristol Laboratories, and RacheUe Laboratories. There are also several manufacturers abroad. Tetracycline is now sold genetically by many companies. Pfizer s doxycycline (6) and Ledede s minocycline (7), both semisynthetic tetracyclines, are the only members of the group that have increasing sales. Table 1 fists the commercial tetracyclines and the corresponding trade names. 

A practical process had earlier been developed for the transformation of chlortetracycline (2) into tetracycline (1) by catalytic hydrogenolysis of the aromatic chloro group. Application of the reaction under suitable conditions to demethylchlortetra-... 

Similar transformations have not as yet been successfully applied to the tetracyclines bearing a hydroxy group at Cs, and no mutant culture has been reported that biosynthesizes a 6-deoxy-5-oxytetracycline. However, other means have been found to avoid 5a,6-dehydration in this subfamily. Treatment of 3 with N-... 

Treatment of 14 with hydrogen and a catalyst converts it to a mixture of epimeric 6-deoxy-5-oxytetracyclines (15 and 16), each of which is active as an antibiotic. The more active isomer has the natural tetracycline configuration of the methyl group at Ce and is in clinical use as a 6-deoxyoxytetracycline (15). ... 

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