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Abstract
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 well known, especially against bacteria, while against other targets, they are virtually unknown. In other diverse fields 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 to classify the compounds already used in therapy and prepare the schematic structure that includes the next generation of TCs. The second aim of this work is to introduce a new framework for the classification of old and new TCs, using a medicinal chemistry approach to the structure of those drugs. A fully documented Structure-Activity-Relationship (SAR) is presented with the analysis data of antibacterial and nonantibacterial (antifungal, antiviral and anticancer) tetracyclines. The lipophilicity and the conformational interchangeability of the functional groups are employed to develop the rules for TC biological activity.
Highlights
The number of articles published on tetracycline drugs has reached the threshold of 50,000 papers since 1948
The present paper introduces a new schematic point of view about the denomination and the classification of Tetracycline-Structure-Based drugs
In this work a new framework is introduced for the classification of old and novel TCs and their
Summary
The number of articles published on tetracycline drugs has reached the threshold of 50,000 papers since 1948. Tetracyclines (TCs) are a class of antibiotics able to inhibit protein synthesis in gram positive and gram negative bacteria by preventing the attachment of aminoacyl-tRNA to the ribosomal acceptor (A) site [2]. This mechanism has been confirmed by X-ray crystallography [3]. TCs belong to a notable class of biologically active and commercially valuable compounds This fact may be illustrated by mentioning the most important clinical application of TCs, their employment as broad antimicrobial-spectrum antibiotics for human and veterinary use [4]
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