Therapy
Tetracyclines: Nonantibiotic properties and their clinical implications

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Tetracyclines are broad-spectrum antibiotics that act as such at the ribosomal level where they interfere with protein synthesis. They were first widely prescribed by dermatologists in the early 1950s when it was discovered that they were effective as a treatment for acne. More recently, biologic actions affecting inflammation, proteolysis, angiogenesis, apoptosis, metal chelation, ionophoresis, and bone metabolism have been researched. The therapeutic effects of tetracycline and its analogues in various diseases have also been investigated. These include rosacea, bullous dermatoses, neutrophilic diseases, pyoderma gangrenosum, sarcoidosis, aortic aneurysms, cancer metastasis, periodontitis, and autoimmune disorders such as rheumatoid arthritis and scleroderma. We review the nonantibiotic properties of tetracycline and its analogues and their potential for clinical application.

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Chemistry

Tetracyclines and analogues with biological effects on bacteria and mammalian targets show a basic chemical structure consisting of a tetracyclic naphthacene carboxamide ring system (Fig 1). Tetracyclines with antibiotic activity have a dimethylamine group at carbon 4 (C4) in ring A. Removal of the dimethylamino group from C4 reduces its antibiotic properties, but enhances nonantibiotic actions.3 Utilization of this strategy was the basis for the development of several chemically modified

Tetracyclines as ionophores

Ionophores are organic compounds capable of forming lipid-soluble complexes with metal cations.7 Transportation of these cations across hydrophobic barriers, such as artificial or biological membranes, is an important function of these compounds. Tetracyclines bind divalent metal cations, mostly along the lower peripheral region, and circulate in blood plasma primarily as Ca++ and Mg++ chelates.3 Their role as calcium ionophores has important biologic implications. After its intracellular

Nonantibiotic properties of tetracyclines

The nonantibiotic properties of tetracyclines are summarized in Fig 2 and discussed in detail below.

Clinical studies

Diseases, both dermatologic and nondermatologic, that have been investigated for the therapeutic use of tetracyclines are listed in Table II.

Conclusions

Tetracycline and its analogues have been used in the treatment of various dermatologic and nondermatologic diseases. Although there is some evidence for anti-inflammatory and immunomodulatory effects, additional studies must be performed, at both the laboratory and clinical levels, to corroborate these properties.

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    Conflicts of interest: None identified.

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