Tackling Drug-Resistant Tuberculosis: Current Trends and Approaches

Jun 10, 2016Mini reviews in medicinal chemistry

Current Trends and Strategies for Fighting Drug-Resistant Tuberculosis

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Abstract

Over 1.5 million deaths annually are attributed to tuberculosis, highlighting the urgent need for new treatment approaches.

The emergence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) strains complicates tuberculosis management.
An increase in HIV cases and latent tuberculosis contributes to the persistence of the disease.
Various new molecules are being developed to address drug resistance, including derivatives of fluoroquinolones and rifamycins.
The review outlines the historical development of tuberculosis drugs and their mechanisms of action.
Challenges and bottlenecks in tuberculosis drug development are discussed, along with the potential of nanoscience in treatment.

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Tuberculosis is very much rampant in our society and accounts for a large number of deaths annually. In spite of consistent efforts being made, the disease has not been curtailed yet. The emergence of MDR and XDR strains in the society along with an increase in the number of HIV cases and that of latent TB, have further aggravated the problem making the disease very much persistent. The current situation clearly manifests the need to discover and develop new potent molecules/approaches that could help to tackle drug resistance. Various molecules, such as derivatives of fluoroquinolones (e.g. gatifloxacin, moxifloxacin and DC-159a), rifamycins (rifapentine), oxazolidinones (linezolid, sutezolid/PNU-100480), diarylquinolines (TMC207/bedaquiline), antifungal azoles, pyrrole (LL3858), nitroimidazopyran (PA824), nitroimidazole (OPC67683, TBA-354), diamine (SQ109) and benzothiazinone (BTZ043) are being developed in an attempt to combat the disease. This review presents a general introduction to the current status of the disease, the biology of the pathogen as well as the state of drug development against tuberculosis (TB) with emphasis on the major problems and bottlenecks associated with the same. Starting from the first drug against TB, the review discusses the entire history and the course of development of the drugs which are available today in the market as well as those which are under various phases of clinical and pre-clinical trials along with their mechanism of action. It also talks about the possible role of nanosciences in combating TB.

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