Classification Framework and Structure-Activity-Relationship (SAR) of Tetracycline-Structure-Based Drugs

By studying the literature about Tetracyclines (TCs), it becomes clearly evident that TCs are very dynamic molecules. In some cases, their structure-activity-relationship (SAR) are known, especially against bacteria, while against other targets, they are virtually unknown. In other diverse yields of research, such as neurology, oncology and virology the utility and activity of the tetracyclines are being discovered and are also emerging as new technological fronts. The first aim of this paper is classify the compounds already used in therapy and prepare the schematic structure in which include the next generation of TCs. The aim of this work is introduce a new framework for the classification of old and new TCs, using a medicinal chemistry approach to the structure of that drugs. A fully documented Structure-Activity-Relationship (SAR) is presented with the analysis data of antibacterial and nonantibacterial (antifungal, antiviral and anticancer) tetracyclines. Lipophilicity of functional groups and conformations interchangeably are determining rules in biological activities of TCs.Comment: 13 pages, 3 figures, 2 schemes, 1 table; http://www.mdpi.com/2079-6382/1/1/

Tetracycline Actions Relevant to Rosacea Treatment

Until today, the pathogenesis of rosacea is not known in detail. Yet in recent years evidence has been accumulating that rosacea with its common symptoms such as inflammatory lesions, erythema, telangiectasia, phymatous changes, and ocular symptoms is of inflammatory nature. Tetracycline derivatives like doxycycline successfully used in the treatment of skin diseases like acne and rosacea seem to inhibit different inflammatory pathways involved in the pathogenesis by various modes of action. Although data for skin diseases are relatively scanty, the following modes of action of tetracyclines seem to be most relevant for an effective treatment of acne and rosacea: inhibition of matrix metalloproteinases, downmodulation of cytokines, inhibition of cell movement and proliferation, inhibition of granuloma formation, inhibition of reactive oxygen species, nitric oxide, and angiogenesis, whereas inhibition of phospholipase A2 seems to be of lower importance. The role of the saprophytic mite Demodex folliculorum remains to be clarified. Additional studies are necessary to further elucidate how tetracyclines work in rosacea treatment. Copyright (C) 2009 S. Karger AG, Base

Proficiency test for antibiotics in bovine muscle

The aim of this proficiency study was to give laboratories the possibility to evaluate or demonstrate their competence for the analysis of antibiotics in bovine muscle, including the screening analysis. This study also provided an evaluation of the methods applied for screening and quantitative confirmatory analysis of antibiotics in bovine muscle

Doxycycline alters metabolism and proliferation of human cell lines.

The tetracycline antibiotics are widely used in biomedical research as mediators of inducible gene expression systems. Despite many known effects of tetracyclines on mammalian cells-including inhibition of the mitochondrial ribosome-there have been few reports on potential off-target effects at concentrations commonly used in inducible systems. Here, we report that in human cell lines, commonly used concentrations of doxycycline change gene expression patterns and concomitantly shift metabolism towards a more glycolytic phenotype, evidenced by increased lactate secretion and reduced oxygen consumption. We also show that these concentrations are sufficient to slow proliferation. These findings suggest that researchers using doxycycline in inducible expression systems should design appropriate controls to account for potential confounding effects of the drug on cellular metabolism

Pharmacodynamic modelling of in vitro activity of tetracycline against a representative, naturally occurring population of porcine Escherichia coli

Background The complex relationship between drug concentrations and bacterial growth rates require not only the minimum inhibitory concentration but also other parameters to capture the dynamic nature of the relationship. To analyse this relationship between tetracycline concentration and growth of Escherichia coli representative of those found in the Danish pig population, we compared the growth of 50 randomly selected strains. The observed net growth rates were used to describe the in vitro pharmacodynamic relationship between drug concentration and net growth rate based on E max model with three parameters: maximum net growth rate (α max ); concentration for a half-maximal response (E max ); and the Hill coefficient (γ). Results The net growth rate in the absence of antibiotic did not differ between susceptible and resistant isolates (P = 0.97). The net growth rate decreased with increasing tetracycline concentrations, and this decline was greater in susceptible strains than resistant strains. The lag phase, defined as the time needed for the strain to reach an OD 600 value of 0.01, increased exponentially with increasing tetracycline concentration. The pharmacodynamic parameters confirmed that the αmax between susceptible and resistant strains in the absence of a drug was not different. EC 50 increased linearly with MIC on a log–log scale, and γ was different between susceptible and resistant strains. Conclusions The in vitro model parameters described the inhibition effect of tetracycline on E. coli when strains were exposed to a wide range of tetracycline concentrations. These parameters, along with in vivo pharmacokinetic data, may be useful in mathematical models to predict in vivo competitive growth of many different strains and for development of optimal dosing regimens for preventing selection of resistance