Potential Repurposed Drug Candidates for Tuberculosis Treatment: Progress and Update of Drugs Identified in Over a Decade

Abstract

The devastating impact of Tuberculosis (TB) has been a menace to mankind for decades. The World Health Organization (WHO) End TB Strategy aims to reduce TB mortality up to 95% and 90% of overall TB cases worldwide, by 2035. This incessant urge will be achieved with a breakthrough in either a new TB vaccine or novel drugs with higher efficacy. However, the development of novel drugs is a laborious process involving a timeline of almost 20−30 years with huge expenditure; on the other hand, repurposing previously approved drugs is a viable technique for overcoming current bottlenecks in the identification of new anti-TB agents. The present comprehensive review discusses the progress of almost all the repurposed drugs that have been identified to the present day (∼100) and are in the development or clinical testing phase against TB. We have also emphasized the efficacy of repurposed drugs in combination with already available frontline anti-TB medications along with the scope of future investigations. This study would provide the researchers a detailed overview of nearly all identified anti-TB repurposed drugs and may assist them in selecting the lead compounds for further in vivo/clinical research.

Overcoming Mycobacterium tuberculosis Drug Resistance: Novel Medications and Repositioning Strategies

“…In vitro tests have demonstrated its ability to stop the growth of mycobacteria and cooperate with other anti-TB drugs. Preclinical studies in animal models have shown its efficacy in reducing the bacterial burden and increasing lung pathology in TB infection Disulfiram: Originally used to treat alcoholism, disulfiram has been identified as a potential treatment for tuberculosis.…”

Repurposing Azoles to Resolve Serotogenic Toxicity Associated with Linezolid to Combat Multidrug-Resistant Tuberculosis

“…Similarly, the anti-mycobacterial characteristics of medications used to treat infections caused by viruses and unicellular prokaryotic and eukaryotic organisms have been thoroughly investigated. 14 Taken together, we hypothesized that azole antifungals may be of therapeutic value for the treatment of TB. 10,14 One key reason for this notion is their structural similarity, conveying the 3D structural resemblance between azole antifungals and Linezolid (Figure 1).…”

“…14 Taken together, we hypothesized that azole antifungals may be of therapeutic value for the treatment of TB. 10,14 One key reason for this notion is their structural similarity, conveying the 3D structural resemblance between azole antifungals and Linezolid (Figure 1). Like the 2-oxazolidinone ring A of Linezolid, Itraconazole and Posaconazole contain an isosteric 1,2,4-triazol-3-one ring B.…”

“…11−13 Over the years, various studies and trials have been undertaken with the aim of repurposing existing drugs to address the bottleneck in the development of novel anti-TB agents. 14 The notion of ″spectrum expansion″ underpins the repurposing of antiinfective drugs, in which a chemical with broad-spectrum activity and efficacy against one disease (for example, bacterial species) is tested against another pathogen. 14 Since Mtb is a bacterial species, several broad-spectrum antibacterial treatments have been shown to be effective against TB.…”

“…14 The notion of ″spectrum expansion″ underpins the repurposing of antiinfective drugs, in which a chemical with broad-spectrum activity and efficacy against one disease (for example, bacterial species) is tested against another pathogen. 14 Since Mtb is a bacterial species, several broad-spectrum antibacterial treatments have been shown to be effective against TB. Similarly, the anti-mycobacterial characteristics of medications used to treat infections caused by viruses and unicellular prokaryotic and eukaryotic organisms have been thoroughly investigated.…”