AN EXHAUSTIVE REVIEW ON EMERGING DRUG TARGETS OF TUBERCULOSIS WITH SPECIAL EMPHASIS ON CELL WALL SYNTHESIS

Tuberculosis (TB) is one of the top 10 causes of mortality and morbidity. Worldwide, yet, it has been over 60 years since a novel drug was introduced in market to treat the disease exclusively. Increased number of drug resistant TB cases has prompted the search for novel potent anti-TB drug. Mycobacterial cell wall has unique structure which provides integrity to the cell. The future development of new potent anti-TB drug targets is associated with the synthesis of various cell wall constituents; the structural and genetic information about mycobacterial cell wall envelope is now available. In the present review, we have focused on prospective drug targets that can be optimum triumph for successful drug candidate.

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Mycobacterial cell wall biosynthesis: a multifaceted antibiotic target

Parasitology ◽

10.1017/s0031182016002377 ◽

2016 ◽

Vol 145 (2) ◽

pp. 116-133 ◽

Cited By ~ 51

Author(s):

KATHERINE A. ABRAHAMS ◽

GURDYAL S. BESRA

Keyword(s):

Cell Wall ◽

Drug Targets ◽

Complex Structure ◽

Supporting Cell ◽

Chemotherapeutic Agents ◽

World Health ◽

Mycobacterial Cell ◽

Clinical Drugs ◽

Health Organization ◽

Mycobacterial Cell Wall

SUMMARYMycobacterium tuberculosis(Mtb), the etiological agent of tuberculosis (TB), is recognized as a global health emergency as promoted by the World Health Organization. Over 1 million deathsperyear, along with the emergence of multi- and extensively-drug resistant strains ofMtb, have triggered intensive research into the pathogenicity and biochemistry of this microorganism, guiding the development of anti-TB chemotherapeutic agents. The essential mycobacterial cell wall, sharing some common features with all bacteria, represents an apparent ‘Achilles heel’ that has been targeted by TB chemotherapy since the advent of TB treatment. This complex structure composed of three distinct layers, peptidoglycan, arabinogalactan and mycolic acids, is vital in supporting cell growth, virulence and providing a barrier to antibiotics. The fundamental nature of cell wall synthesis and assembly has rendered the mycobacterial cell wall as the most widely exploited target of anti-TB drugs. This review provides an overview of the biosynthesis of the prominent cell wall components, highlighting the inhibitory mechanisms of existing clinical drugs and illustrating the potential of other unexploited enzymes as future drug targets.

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Potential Drug Targets in Mycobacterial Cell Wall: Non-Lipid Perspective

Current Drug Discovery Technologies ◽

10.2174/1570163815666180605113609 ◽

2020 ◽

Vol 17 (2) ◽

pp. 147-153

Author(s):

Shrayanee Das ◽

Saif Hameed ◽

Zeeshan Fatima

Keyword(s):

Cell Wall ◽

Drug Targets ◽

Cell Structure ◽

Front Line ◽

New Drug ◽

Mycobacterial Cell ◽

Future Drug ◽

Mycobacterial Cell Wall ◽

Potential Drug Targets ◽

Wall Components

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB), still remains a deadly disease worldwide. With prolonged usage of anti-TB drugs, the current therapeutic regimes are becoming ineffective, particularly due to emergence of drug resistance in MTB. Under such compelling circumstances, it is pertinent to look for new drug targets. The cell wall envelope of MTB is composed of unique lipids that are frequently targeted for anti-TB therapy. This is evident from the fact that most of the commonly used front line drugs (Isoniazid and Ethambutol) act on lipid machinery of MTB. Thus, despite the fact that much of the attention is towards understanding the MTB lipid biology, in search for identification of new drug targets, our knowledge of bacterial cell wall non-lipid components remains rudimentary and underappreciated. Better understanding of such components of mycobacterial cell structure will help in the identification of new drug targets that can be utilized on the persistent mycobacterium. This review at a common platform summarizes some of the non-lipid cell wall components in MTB that have potential to be exploited as future drug targets.

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Drug-Resistant Tuberculosis and Inhibition of Biosynthetic Enzymes for Polysaccharides in Mycobacterial Cell Wall

Trends in Glycoscience and Glycotechnology ◽

10.4052/tigg.23.106 ◽

2011 ◽

Vol 23 (130) ◽

pp. 106-107

Author(s):

Akihiro Ishiwata

Keyword(s):

Cell Wall ◽

Biosynthetic Enzymes ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Resistant Tuberculosis ◽

Mycobacterial Cell ◽

Mycobacterial Cell Wall

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714: Inhibition of Bladder Cancer Cell Proliferation by Mycobacterial Cell Wall-DNA Complex (MCC) in Combination with Chemotherapeutic Agents

The Journal of Urology ◽

10.1016/s0022-5347(18)37963-1 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 190-190

Author(s):

Myriam Labelle ◽

Mario C. Filion ◽

Nigel C. Phillips

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Cell Wall ◽

Cancer Cell ◽

Chemotherapeutic Agents ◽

Bladder Cancer Cell ◽

Cancer Cell Proliferation ◽

Mycobacterial Cell ◽

Mycobacterial Cell Wall ◽

Dna Complex

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Anti-tubercular activity of some six membered heterocycle compounds

10.31221/osf.io/uk9bn ◽

2019 ◽

Author(s):

Chem Int

Keyword(s):

Infectious Disease ◽

Cell Wall ◽

Latent Tuberculosis ◽

Drug Resistant ◽

Significant Development ◽

Tb Treatment ◽

Modern Drug ◽

Mycobacterial Cell Wall ◽

Membered Heterocycle ◽

New Chemical Entity

The effectiveness in TB treatment is difficult because the structural composition of the mycobacterial cell wall is very complicated, which makes many drugs ineffective. Tuberculosis is still one of the most imperative infectious disease worldwide becouse its important reason is drug resistant, persistent or latent tuberculosis and synergism with HIV. Furthermore no any new chemical entity has come. The recently application of modern drug design promise to bring significant development in the fight against TB. In present review we discussed brief introduction of tuberculosis.

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