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

TL;DR

This paper introduces a new classification framework for tetracycline drugs based on medicinal chemistry principles and presents a detailed SAR analysis across antibacterial and other therapeutic activities.

Contribution

It develops a novel classification framework for tetracyclines and provides a comprehensive SAR analysis including structural and lipophilicity factors influencing activity.

Findings

Lipophilicity influences biological activity of TCs.

Structural conformations are key to activity.

New tetracycline classes are proposed.

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 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.