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Review
. 2021 May 13;14(5):461.
doi: 10.3390/ph14050461.

Chemical Classes Presenting Novel Antituberculosis Agents Currently in Different Phases of Drug Development: A 2010-2020 Review

Klaudia T Angula  1 , Lesetja J Legoabe  1 , Richard M Beteck  1
Affiliations
Review

Chemical Classes Presenting Novel Antituberculosis Agents Currently in Different Phases of Drug Development: A 2010-2020 Review

Klaudia T Angula et al. Pharmaceuticals (Basel). .

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a curable airborne disease currently treated using a drug regimen consisting of four drugs. Global TB control has been a persistent challenge for many decades due to the emergence of drug-resistant Mtb strains. The duration and complexity of TB treatment are the main issues leading to treatment failures. Other challenges faced by currently deployed TB regimens include drug-drug interactions, miss-matched pharmacokinetics parameters of drugs in a regimen, and lack of activity against slow replicating sub-population. These challenges underpin the continuous search for novel TB drugs and treatment regimens. This review summarizes new TB drugs/drug candidates under development with emphasis on their chemical classes, biological targets, mode of resistance generation, and pharmacokinetic properties. As effective TB treatment requires a combination of drugs, the issue of drug-drug interaction is, therefore, of great concern; herein, we have compiled drug-drug interaction reports, as well as efficacy reports for drug combinations studies involving antitubercular agents in clinical development.

Keywords: diarylquinolines; drug development; fluoroquinolones; nitroimidazoles; pharmacokinetics; tuberculosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
TB drugs and drug candidates and their associated targets.
Figure 1
Figure 1
The chemical structures of potential anti-TB fluoroquinolones.
Figure 2
Figure 2
The chemical structures of diarylquinoline analogs in TB clinical studies.
Figure 3
Figure 3
The chemical structure of nitroimidazoles undergoing clinical development as TB drugs.
Figure 4
Figure 4
The chemical structures of oxazolidinones currently in TB clinical trials.
Figure 5
Figure 5
The chemical structure of SQ-109.
Figure 6
Figure 6
The structures of Q203 and its analogs (TB47 and ND-11543) that show potential as novel TB agents.
Figure 7
Figure 7
The chemical structures of novel DprE1 inhibitors under clinical development for Mtb treatment.
Figure 8
Figure 8
The chemical structure of CPZEN-45, a potential drug candidate for TB therapy.
Figure 9
Figure 9
The chemical structures of riminophenazines: CFZ and TBI-166 with potential anti-TB properties.
Figure 10
Figure 10
The chemical structures of pyrrole drug candidates being investigated for TB treatment.
Figure 11
Figure 11
The chemical structures of GSK-693 and NITD-916; novel direct Mtb InhA inhibitors.
Figure 12
Figure 12
The chemical structures of faropenem and ertapenem.
Figure 13
Figure 13
The chemical structure of GSK-070, an oxoborate drug in TB clinical trials.
See this image and copyright information in PMC

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