Repurposing drugs for treatment of tuberculosis: a role for non-steroidal anti-inflammatory drugs

Abstract

Introduction: The number of cases of drug-resistant Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), has risen rapidly in recent years. This has led to the resurgence in repurposing existing drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs), for anti-TB treatment.

Sources of data: Evidence from novel drug screening in vitro, in vivo, pharmacokinetic/pharmacodynamics analyses and clinical trials has been used for the preparation of this systematic review of the potential of NSAIDs for use as an adjunct in new TB chemotherapies.

Areas of agreement: Certain NSAIDs have demonstrated inhibitory properties towards actively replicating, dormant and drug-resistant clinical isolates of M. tuberculosis cells.

Areas of controversy: NSAIDs are a diverse class of drugs, which have reported off-target activities, and their endogenous antimicrobial mechanism(s) of action is still unclear.

Growing points: It is essential that clinical trials of NSAIDs continue, in order to assess their suitability for addition to the current TB treatment regimen. Repurposing molecules such as NSAIDs is a vital, low-risk strategy to combat the trend of rapidly increasing antibiotic resistance.

Keywords: Mycobacterium; NSAIDs; antimicrobial resistance; carprofen; drug repurposing; tuberculosis.

Fig. 1

The possible endogenous mechanisms of action of repurposed drugs. The drugs and their targets are highlighted in lighter and darker shaded boxes, respectively. The anagram MAGP is used to indicate the ’mycolic acid–arabinogalactan–peptidoglycan’ layer of the mycobacterial cell wall and PBP refers to the penicillin-binding proteins responsible for the maturation of the cell wall peptidoglycan.

Fig. 2

Chemical classes and the structures of the various NSAIDs under investigation for their antimicrobial properties.