An overview of new antitubercular drugs, drug candidates, and their targets

The causative agent of tuberculosis (TB), Mycobacterium tuberculosis and more recently totally drug‐resistant strains of M. tuberculosis, display unique mechanisms to survive in the host. A four‐drug treatment regimen was introduced 40 years ago but the emergence of multidrug‐resistance and more rec...

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Published inMedicinal research reviews Vol. 40; no. 1; pp. 263 - 292
Main Authors Bahuguna, Aparna, Rawat, Diwan S.
Format Journal Article
LanguageEnglish
Published United States Wiley Subscription Services, Inc 01.01.2020
Subjects
Antibiotics
bedaquiline
clofazimine
delamanid
delpazolid
Drug development
Drugs
FDA approval
levofloxacin
linezolid
moxifloxacin
PBTZ169
pretomanid
SQ109
structure‐activity relationship
sutezolid
Tuberculosis
sutezolid
linezolid
clofazimine
levofloxacin
PBTZ169
delamanid
SQ109
pretomanid
delpazolid
bedaquiline
structure-activity relationship
moxifloxacin
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Summary:The causative agent of tuberculosis (TB), Mycobacterium tuberculosis and more recently totally drug‐resistant strains of M. tuberculosis, display unique mechanisms to survive in the host. A four‐drug treatment regimen was introduced 40 years ago but the emergence of multidrug‐resistance and more recently TDR necessitates the identification of new targets and drugs for the cure of M. tuberculosis infection. The current efforts in the drug development process are insufficient to completely eradicate the TB epidemic. For almost five decades the TB drug development process remained stagnant. The last 10 years have made sudden progress giving some new and highly promising drugs including bedaquiline, delamanid, and pretomanid. Many of the candidates are repurposed compounds, which were developed to treat other infections but later, exhibited anti‐TB properties also. Each class of drug has a specific target and a definite mode of action. These targets are either involved in cell wall biosynthesis, protein synthesis, DNA/RNA synthesis, or metabolism. This review discusses recent progress in the discovery of newly developed and Food and Drug Administration approved drugs as well as repurposed drugs, their targets, mode of action, drug‐target interactions, and their structure‐activity relationship.
ISSN:0198-6325
1098-1128
DOI:10.1002/med.21602