Abstract
It is estimated that a third of the worlds population is currently infected with tuberculosis, leading to 1.6 million deaths annually. The current drug regimen is 40 years old and takes 6-9 months to administer. In addition, the emergence of drug resistant strains and HIV co-infection mean that there is an urgent need for new anti-tuberculosis drugs. The twenty-first century has seen a revival in research and development activity in this area, with several new drug candidates entering clinical trials. This review considers new potential firstline anti-tuberculosis drug candidates, in particular those with novel mechanisms of action, as these are most likely to prove effective against resistant strains. A brief overview of current first-line and recent drugs (such as fluoroquinolones, rifampicin and isoniazid analogues) is initially presented. This is followed by a description of structure-activity relationships, in vitro and in vivo activity, pharmacokinetics, mechanism of action, combination regimens and clinical trials of the new drug candidates SQ109, PA-824, OPC-67683, TMC207 and others.
Keywords: Mycobacterium tuberculosis, drug action, SQ109, PA-824, OPC-67683, TMC207/R207910
Current Medicinal Chemistry
Title: New Anti-Tuberculosis Drugs with Novel Mechanisms of Action
Volume: 15 Issue: 19
Author(s): Emma C. Rivers and Ricardo L. Mancera
Affiliation:
Keywords: Mycobacterium tuberculosis, drug action, SQ109, PA-824, OPC-67683, TMC207/R207910
Abstract: It is estimated that a third of the worlds population is currently infected with tuberculosis, leading to 1.6 million deaths annually. The current drug regimen is 40 years old and takes 6-9 months to administer. In addition, the emergence of drug resistant strains and HIV co-infection mean that there is an urgent need for new anti-tuberculosis drugs. The twenty-first century has seen a revival in research and development activity in this area, with several new drug candidates entering clinical trials. This review considers new potential firstline anti-tuberculosis drug candidates, in particular those with novel mechanisms of action, as these are most likely to prove effective against resistant strains. A brief overview of current first-line and recent drugs (such as fluoroquinolones, rifampicin and isoniazid analogues) is initially presented. This is followed by a description of structure-activity relationships, in vitro and in vivo activity, pharmacokinetics, mechanism of action, combination regimens and clinical trials of the new drug candidates SQ109, PA-824, OPC-67683, TMC207 and others.
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Cite this article as:
Rivers C. Emma and Mancera L. Ricardo, New Anti-Tuberculosis Drugs with Novel Mechanisms of Action, Current Medicinal Chemistry 2008; 15 (19) . https://dx.doi.org/10.2174/092986708785132906
DOI https://dx.doi.org/10.2174/092986708785132906 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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