Bedaquiline: A Novel Diarylquinoline for Multidrug-Resistant Pulmonary Tuberculosis

Deshkar, Anuradha T; Shirure, Prashant A.

doi:10.7759/cureus.28519

Cited by 5 publications

(2 citation statements)

References 34 publications

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“…The development of compounds that target energy metabolism enzymes in M. tuberculosis , such as the respiratory chain complexes and F 1 ∙F o , is now considered a new promising strategy. Bedaquiline (TMC207, BDQ, Sirturo™) was the first drug approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), which belongs to the class of bioenergetics inhibitors [ 114 , 115 , 116 , 117 ]. It is a diarylquinoline derivative having a quinolinic central heterocyclic nucleus with alcohol and amine side chains ( Figure 4 , left structure) which are suggested to play a significant role in anti-tuberculosis activity [ 115 , 118 ].…”

Section: Mycobacterium Tuberculosis F 1 ∙...mentioning

confidence: 99%

F1·Fo ATP Synthase/ATPase: Contemporary View on Unidirectional Catalysis

Zharova

Grivennikova

Borisov

2023

IJMS

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F1·Fo-ATP synthases/ATPases (F1·Fo) are molecular machines that couple either ATP synthesis from ADP and phosphate or ATP hydrolysis to the consumption or production of a transmembrane electrochemical gradient of protons. Currently, in view of the spread of drug-resistant disease-causing strains, there is an increasing interest in F1·Fo as new targets for antimicrobial drugs, in particular, anti-tuberculosis drugs, and inhibitors of these membrane proteins are being considered in this capacity. However, the specific drug search is hampered by the complex mechanism of regulation of F1·Fo in bacteria, in particular, in mycobacteria: the enzyme efficiently synthesizes ATP, but is not capable of ATP hydrolysis. In this review, we consider the current state of the problem of “unidirectional” F1·Fo catalysis found in a wide range of bacterial F1·Fo and enzymes from other organisms, the understanding of which will be useful for developing a strategy for the search for new drugs that selectively disrupt the energy production of bacterial cells.

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Section: Mycobacterium Tuberculosis F 1 ∙...mentioning

confidence: 99%

F1·Fo ATP Synthase/ATPase: Contemporary View on Unidirectional Catalysis

Zharova

Grivennikova

Borisov

2023

IJMS

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“…Several compounds have been identified during the last few years with potential anti-tubular properties and are currently undergoing preclinical and clinical studies like, bedaquiline ( Antoci et al, 2021 ; Chakraborti et al, 2021 ; Patil & Jain, 2021 ; Deshkar & Shirure, 2022 ), PA-824 ( Lenaerts et al, 2005 ; Edwards & Field, 2022 ; Xu et al, 2022 ; Yan et al, 2022 ), and delamanid ( Skripconoka et al, 2013 ; Liu et al, 2018 ; Nasiri et al, 2022 ). Existing drugs have also been modified to repurpose them against TB and they include -riminophenazines ( Valinetz et al, 2020 ; Brunaugh et al, 2022 ), b-lactams ( Moon et al, 2018 ; Story-Roller & Lamichhane, 2018 ; Ur Rahman et al, 2018 ), and oxazolidinones ( Balasubramanian et al, 2014 ; Alghamdi et al, 2020 ; Margaryan et al, 2022 ; Ndukwe et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Advances in computational frameworks in the fight against TB: The way forward

Naidu

Nayak

et al. 2023

Front. Pharmacol.

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Around 1.6 million people lost their life to Tuberculosis in 2021 according to WHO estimates. Although an intensive treatment plan exists against the causal agent, Mycobacterium Tuberculosis, evolution of multi-drug resistant strains of the pathogen puts a large number of global populations at risk. Vaccine which can induce long-term protection is still in the making with many candidates currently in different phases of clinical trials. The COVID-19 pandemic has further aggravated the adversities by affecting early TB diagnosis and treatment. Yet, WHO remains adamant on its “End TB” strategy and aims to substantially reduce TB incidence and deaths by the year 2035. Such an ambitious goal would require a multi-sectoral approach which would greatly benefit from the latest computational advancements. To highlight the progress of these tools against TB, through this review, we summarize recent studies which have used advanced computational tools and algorithms for—early TB diagnosis, anti-mycobacterium drug discovery and in the designing of the next-generation of TB vaccines. At the end, we give an insight on other computational tools and Machine Learning approaches which have successfully been applied in biomedical research and discuss their prospects and applications against TB.

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