An Integration of Interdisciplinary Translational Research in Anti-TB Drug Discovery: Out of the University Research Laboratories to Combat Mycobacterium tuberculosis

Bhakta, Sanjib

doi:10.4172/2168-9547.1000e108

Cited by 6 publications

(4 citation statements)

References 33 publications

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“…• They have single sub-therapeutic doses given to 10 to 15 volunteers and give pharmacokinetic data or help with imaging specific targets without exerting pharmacological actions 48 .…”

Section: Fig 2: Stages Of Drug Discovery Preclinical Researchmentioning

confidence: 99%

Untitled

2023

IJPSR

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Drug discovery is a process that aims at identifying a compound therapeutically useful in curing and treating disease. This process involves the identification of candidates, synthesis, characterization, validation, optimization, screening, and assays for therapeutic efficacy. Once a compound has shown its significance in these investigations, it will initiate the drug development process earlier to clinical trials. The new drug development process must continue through several stages to make a safe, effective medicine that has approved all regulatory requirements. One overall theme of our article is that the process is sufficiently long, complex, and expensive, so many biological targets must be considered for every new medicine ultimately approved for clinical use, and new research tools may be needed to investigate each new target. From initial discovery to a marketable medicine is a long, challenging task. It takes about 12 -15 years from discovery to the approved medication and requires an investment of about USD 1 billion. This article outlines the processes of new drug discovery and development.INTRODUCTION: Drug discovery is the process through which potential new medicines are identified. It involves a wide range of scientific disciplines, including biology, chemistry, and pharmacology 1-2 . In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered. Historically, drugs were discovered by identifying the active ingredient from traditional remedies or serendipitous discovery, as with penicillin 3 .

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“…• They have single sub-therapeutic doses given to 10 to 15 volunteers and give pharmacokinetic data or help with imaging specific targets without exerting pharmacological actions 48 .…”

Section: Fig 2: Stages Of Drug Discovery Preclinical Researchmentioning

confidence: 99%

Untitled

2023

IJPSR

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“…Whole-cell evaluation offers a number of advantages over other drug discovery methods which includes the evaluation of a compounds’ efficiency in penetrating bacterial cell-walls and for discovering novel efflux inhibitors [ 12 ]. In addition, whole-cell evaluation is a sensible platform combined with target drug design for the discovery of compounds that are prodrug which require intracellular metabolism to become active [ 13 ]. Alternative platforms primarily focusing on specific biomolecule targets, disregarding whole-cell screening, have therefore faced several challenges in new antibiotic development.…”

Section: Introductionmentioning

confidence: 99%

Chalcones, stilbenes and ketones have anti-infective properties via inhibition of bacterial drug-efflux and consequential synergism with antimicrobial agents

Hellewell

Bhakta

2020

Access Microbiology

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With antimicrobial resistance creating a major public health crisis, the designing of novel antimicrobial compounds that effectively combat bacterial infection is becoming increasingly critical. Interdisciplinary approaches integrate the best features of whole-cell phenotypic evaluation to validate novel therapeutic targets and discover new leads to combat antimicrobial resistance. In this project, whole-cell phenotypic evaluation such as testing inhibitors on bacterial growth, viability, efflux pump, biofilm formation and their interaction with other drugs were performed on a panel of Gram-positive, Gram-negative and acid-fast group of bacterial species. This enabled additional antimicrobial activities of compounds belonging to the flavonoid family including ketones, chalcones and stilbenes, to be identified. Flavonoids have received renewed attention in literature over the past decade, and a variety of beneficial effects of these compounds have been illuminated, including anti-cancer, anti-inflammatory, anti-tumour as well as anti-fungal and anti-bacterial. However, their mechanisms of action are yet to be identified. In this paper, we found that the compounds belonging to the flavonoid family exerted a range of anti-infective properties being identified as novel efflux pump inhibitors, whilst offering the opportunity to be used in combination therapy. The compound 2-phenylacetophenone displayed broad-spectrum efflux pump inhibition activity, whilst trans-chalcone, displayed potent activity against Gram-negative and mycobacterial efflux pumps causing inhibition higher than known potent efflux pump inhibitors, verapamil and chlorpromazine. Drug-drug interaction studies also highlighted that 2-phenylacetophenone not only has the potential to work additively with known antibacterial agents that affect the cell-wall and DNA replication but also trans-chalcone has the potential to work synergistically with anti-tubercular agents. Overall, this paper shows how whole-cell phenotypic analysis allows for the discovery of new antimicrobial agents and their consequent mode of action whilst offering the opportunity for compounds to be repurposed, in order to contribute in the fight against antimicrobial resistance.

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“…A three-pronged approach of prevention, accurate diagnosis and effective treatment is essential to overcome this disease. 4 However, there are many bottlenecks that impede development in all 3 areas. In the absence of validated, reliable biomarkers to judge the protective efficacy and safety of new vaccine candidates we are left with Bacillus Calmette-Guérin (BCG), the only vaccine available for the last hundred years, even though it falls short of protecting populations against active pulmonary TB.…”

Section: Introductionmentioning

confidence: 99%

Tackling tuberculosis: Insights from an international TB Summit in London

et al. 2015

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Tuberculosis (TB) poses a grave predicament to the world as it is not merely a scientific challenge but a socio-economic burden as well. A prime cause of mortality in human due to an infectious disease; the malady and its cause, Mycobacterium tuberculosis have remained an enigma with many questions that remain unanswered. The ability of the pathogen to survive and switch between varied physiological states necessitates a protracted therapeutic regimen that exerts an excessive strain on low-resource countries. To complicate things further, there has been a significant rise of antimicrobial resistance. Existing control measures, including treatment regimens have remained fairly uniform globally for at least half a century and require reinvention. Overcoming the societal and scientific challenges requires an increase in dialog to identify key regions that need attention and effective partners with whom successful collaborations can be fostered. In this report, we explore the discussions held at the International TB Summit 2015 hosted by EuroSciCon, which served as an excellent platform for researchers to share their recent findings. Ground-breaking results require outreach to affect policy design, governance and control of the disease. Hence, we feel it is important that meetings such as these reach a wider, global audience.

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An Integration of Interdisciplinary Translational Research in Anti-TB Drug Discovery: Out of the University Research Laboratories to Combat Mycobacterium tuberculosis

Cited by 6 publications

References 33 publications

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Chalcones, stilbenes and ketones have anti-infective properties via inhibition of bacterial drug-efflux and consequential synergism with antimicrobial agents

Tackling tuberculosis: Insights from an international TB Summit in London

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