Tetracycline analogs

Free tetracyclines are crystalline amphoteric substances of low solubility. They are available as hydrochlorides, which are more soluble. Such solutions are acid and, with the exception of chlortetracycline, fairly stable. Tetracyclines chelate divalent metal ions, which can interfere with their absorption and activity. A newly approved tetracycline analog, tigecycline, is a glycylcycline and a semisynthetic derivative of minocycline. 

Cammarata compared the Free-Wilson constants derived for a series of tetracycline analogs with some physical constants, and found a relationship which involved two parameters (4). In as yet unpublished work on antimalarial compounds I have found good linear relationships to exist between certain Free-Wilson substituent constants (S.C.) and Hansch s pi or Hammett s sigma constants for the same substituents. These relationships are shown in Table I. 

Synthesis of tetracyclines has been assumed to proceed from a malonamyl-CoA starter unit. There are Streptomyces mutants known to produce tetracycline analogs, for example, 2 acetyl-2-decarboxaraide-(oxy)tetracycltne (Table 1), in which the 2-carbox-... 

Lederet T, Kintrup M, Takahashi M, Sum PE, Ellescad CE, Hillen W. Tetracycline analogs affecting binding to TnJO-encoded Tei repressor trigger the same mechanism of inductiem. Biochem 1996 35 7439-7446. 

The medically useful products demethyltetracycline and doxorubicin (adriamycin) were discovered by simple mutation of the cultures producing tetracycline and daunorubicin (daunomycin), respectively. The tectmique of mutational biosynthesis (mutasynthesis) has been used for the discovery of many new aminoglycoside, macrolide, and anthracycline antibiotics. In this tectmique, a non-producing mutant ( idiotroph ) is isolated and then fed various analogs of the missing moiety. When such a procedure leads to a return of antibiotic activity, it usually is due to the... 

In addition, a total of 21,045 analyses were carried out on samples of bob veal calves using the Calf Antibiotic and Sulfa Test. There were 169 violations including 20 for penicillin, 11 for streptomycin, 29 for tetracycline, 1 for erythromycin, 29 for neomycin, 14 for oxytetracycline, 4 for chlortetracycline, 36 for gentamicin, 14 for sulfamethazine, 6 for sulfamethoxazole, 3 for sulfadimethoxine, and 2 for sulfathiazole. Analogous surveys conducted in 1995 showed 848 violative specimens of the 58,197 samples tested. 

Fru thermore, 156,078 samples from cattle, sheep/lambs, goats, swine, and other animals were screened for antibiotics and sulfonamide drug residues using the fast antimicrobial screen test (FAST) developed in 1991 to replace CAST and STOP. There were 1022 violations for cattle and 2 for swine samples. In cattle, violative cases included 335 for penicillin, 142 for streptomycin, 128 for tetracycline, 28 for erythromycin, 48 for neomycin, 174 for oxytetracycline, 17 for chlortetracycline, 109 for gentamicin, 87 for sulfamethazine, 22 for sulfamethoxazole, 141 for sulfadimethoxine, 7 for sulfachlorpyridazine, 2 for tylosin, and 19 for sulfathiazole. In swine, violative samples were limited to one for oxytetracycline and one for penicillin. Analogous surveys conducted in 1995 showed 804 violative specimens of the 68,139 samples tested. 

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