7-Chlorotetracycline

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. 

Fig. 1. Tetracycline (1) and its derivatives chlortetracycline (7-chlorotetracycline) (2) oxytetracycline (5-hydroxytetracycline) (3), demeclocycline (6-demethyl-7-chlorotetracycline) (4) methacycline (6-demethyl-6-deoxy-5-hydroxy-6-methylenetetracycline) (5) doxycycline (6a-deoxy-5-hydroxytetracycline) (6) and minocycline (6-demethy1-6-deoxy-7-dimethy1 amino tetracycline) (7). Substituents at positions not specifically...

The infection can be cured most readily with tetracycline (7), oxytetracycline (3), or chlorotetracycline (20). Metronidazole (1) and iodoquinol (2) are also effective. Additional effective dmgs include paromomycin (8), tinidazole (11), sulfadiazine (25), and carbarsone [121 -59-4] (31, -ureidobenzenearsonic acid, CyH AsN204, Ameban). 

There are no hiUy effective therapeutic agents for the treatment of thederiasis. Chlorotetracycline (20) and oxytetracycline (3) have therapeutic activity duting the iacubation period. Pamaquiae (68) was reported to have a specific effect on the erythrocyctic forms. Other dmgs with limited efficacy are imidocarb (19) on T annulata halofugiaone (45) on both T annulata and T parva and the naphthoquiaones menoctone (76), parvaquone (88), and buparvaquone (89) on T parva. Methotrexate (90) has been found to be active in vitro (Table 9). 

Aureomycin (7-chlorotetracycline) [57-62-5] M 478.5, m 172-174°(dec), [a] -275° (MeOH), pK 3.3, pK2 7.44, PK3 9.27. Dehydrated by azeotropic distn of its soln with toluene. On cooling anhydrous material crystallises out and is recrystd from CgH, then dried under vacuum at 100° over paraffin wax. (If it is crystd from MeOH, it contains MeOH which is not removed on drying.) [Stephens et al. J Am Chem Soc 76 3568 1954 Biochem Biophys Res Commun 14 137 1964]. 

The contents of the tube were then acidified to pH 2 by the addition of sulfuric acid and centrifuged. Examination of the supernatant liquid by paper chromatography employing the methods of 8ohonos et al. Antibiotics Annual (1953-4, page 49), demonstrates the presence of 7-chloro-6-demethyltetracycline, 7-chlorotetracycline and tetracycline. 

Studies using chlorotetracycline, a dye that detects membrane-bound calcium within cells, show that part of the signal results from release of intracellularly sequestered calcium. Thus, in neutrophils, hyperosmolality inhibits not only exocytosis but also the calcium signal that initiates exocytosis. 

Figure 1. Structures of the fluorescent calcium probes indo-1 and chlorotetracycline.

Figure 3. Reporting of intracellular calcium sequestration by chlorotetracycline (CTC). CTC preferentially partitions into cell membranes and its fluorescence in this environment is sensitive to calcium bound to the membrane therefore its signal (excitation AOO nm, emission 530 nm) will come largely from organelles that bind or sequester calcium, such as smooth endoplasmic reticulum or mitochondria. Release of calcium from such organelles is accompanied by dissociation of the calcium-CTC complex, a decrease in CTC fluorescence and efflux of unbound probe from the organelle and from the cell.

Tetracycline (h/ f 35-40) produced blue and doxycycline (h/fj 15-20), chlorotetracycline (h/ f 25-30) and oxytetracycline (h/fj 40-45) produced violet chromatogram zones on a yellow background. The detection limits for all 4 compounds were 2 ng substance per chromatogram zone (X = 550 nm). 

Tetracycline and several related antibiotics (aureomycin = chlorotetracycline, terramycin — oxytetracycline dihydrate) are also obtained from various species of Streptomyces, but are of very different structure, being based on the fused polycyclic arene naphthacene. The presence of five hydroxy substituents (six for terramycin) and an NMe2 group, and possibilities for various conformations and tautomers, complicate the study of their... 

On the other hand, the analgesic phenylbutazone, the antidepressant paroxetine, tetracycline antibiotics doxycycline and chlorotetracycline, the antibiotics tilmico-sin, danofloxacin, enoxacin, nifuroxazide, the (3-blockers betaxolol, carazolol, pindolol, the (3-agonist clenbuterol, barbiturates, the antihypertensive lisinopril, and the drug to treat cancer tamoxifen were never detected. 

The broad-spectrum antibiotic chlorotetracycline and the aminoglycoside antibiotic kanamycin are observed to lower the cholesterol levels by forming salts with bile acids (e.g.. cholic acid, deoxycholic acid and chenodeoxycholic acid) in the intestinal canal,... 

For electron-rich substrates, nature often uses flavin-dependent halogenases (e.g. chlorotetracycline), vanadium haloperoxidases (snyderol, Figure 7.4) or heme-iron haloperoxidases (tetraiodothyronine. Figure 7.4) for this role (Figure 7.5). For electron-deficient molecules such as alkanes, mononuclear iron... 

Chlorotetracycline Chlorotetracyline, 7-chloro-4-dimethylamino-l,4,4a,5,5a,6,ll,12a-oxtahydro-3,6,10,12,12a-pentahydroxy-6-methyl-1,11 -dioxo-2-naphthacencarboxamide (32.3.1), is obtained biosynthetically as a result of the activity of a miCTOorganism, the actin-omycete S. aureofaciens [196-201]. 

In terms of antibacterial spectrum, this drug is similar to chlorotetracycline. It is used for the same indications. It belongs to the group of short-lasting tetracyclines. Synonyms of this drug are tetramycin, oxymycin, and others. 

Demeclocycline Demeclocycline, 7-chloro-4-dimethylamino-l, 4,4a,5,5a,6,11,12a-octahy-dro-3,6,10,12,12a-pentahdroxy-l,ll-dioxo-2-napthacencarboxamide (32.3.4), is prodnced by a mntant strain of S. aureofaciens, in which the mechanism of transferring methyl gronps is disrapted, and thus demeclocycline or demethylchlorotetracycline differs from chlorotetracycline, oxytetracycline, and tetracycline in the absence of a methyl gronp at Cg of the hydronaphthacene system. As a result, an antibiotic is synthesized that is more resistant to acids and bases in comparison with the methyl homologs [215-221]. 

Target the 30S subunit. Also in this class are Doxycline hyclate oxytetracychne and chlorotetracycline (vibramycin)... 

Zielezny Y., J. Groeneweg, H. Veieecken, and W. Tappe (2006). Impact of sulfadiazine and chlorotetracycline on soil bacterial community structure and respiratory activity. Soil Biology and Biochemistry 38 2372-2380. 

Chlorotetracycline ( Aureomycin) Inhibits root and shoot growth... 

C for 120 hours on a rotary shaker operating at 180 rpm. Upon completion of the fermentation period the mashes were assayed for 7-chlorotetracycline content. 

Fig. 10.26. Separation of some likely components found in commercial tetracycline. (A), Bare capillary with buffer pH 3.0 (30 mM citric acid and 24.5 mM P-alanine) 500 mm x 50 pm i.d. 30 kV, electrokinetic injection for 5 s at 10 kV (B), bare capillary, same as for A but with buffer-methanol (60 40 v/v) (C), Hydride (etched) capillary 250 mm x 50 pm i.d., other conditions same as for B (D), Cl8 etched capillary, conditions same as for C. Peak identification 2, tetracycline 3, chlorotetracycline a, 4-epitetracycline b,...

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