Targeting Multidrug Resistant Mycobacterium tuberculosis HtrA2 with Identical Chemical Entities of Fluoroquinolones

Tuberculosis is a highly communicable and chronic respiratory disease caused by pathogenic bacterium Mycobacterium tuberculosis. The drug - resistant species of Mycobacterium tuberculosis are tough to cure due to its resistant activity toward potential drugs. Available inhibitors of tuberculosis inc...

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Bibliographic Details
Published in:Indian journal of pharmaceutical sciences 2012-05, Vol.74 (3), p.217-222
Main Authors: Daisy, P, Vijayalakshmi, P, Selvaraj, C, Singh, S K, Saipriya, K
Format: Article
Language:English
Subjects:
Antimicrobial agents
Bacteria
Care and treatment
Cell survival
Chaperones
Ciprofloxacin
Drug resistance
Drugs
Excretion
Fluoroquinolones
Macromolecules
Metabolism
Moxifloxacin
Multidrug resistance
Mycobacterium tuberculosis
Ofloxacin
Pharmaceuticals
Pharmacology
Quality control
Quinolone antibacterial agents
Quinolones
Research Paper
Serine proteinase
Temperature effects
Testing
Tuberculosis
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Summary:Tuberculosis is a highly communicable and chronic respiratory disease caused by pathogenic bacterium Mycobacterium tuberculosis. The drug - resistant species of Mycobacterium tuberculosis are tough to cure due to its resistant activity toward potential drugs. Available inhibitors of tuberculosis include few antimicrobial fluoroquinolone agents like ciprofloxacin, ofloxacin, and moxifloxacin to treat resistant Mycobacterium strains. Literature study elucidates that macromolecular target namely, HtrA2 of Mycobacterium tuberculosis play a dual role of protease and chaperone. These two activities are dependent on temperature, with low temperatures promoting the chaperone function and high temperatures promoting serine protease activity. Under normal physiological conditions HtrA2 acts as a quality control factor and promotes cell survival. In the present investigation, we screened fluoroquinolone such as ciprofloxacin, moxifloxacin and ofloxacin and their analogues based on better Docking score, absorption, distribution, metabolism and excretion screening and Lipinski's rule of 5, to find out their efficiency on resistant strain through in silico study. From the results observed, the analogues are suggested to be potent inhibitors of HtrA2 with sufficient scope for further exploration.
ISSN:0250-474X
1998-3743
DOI:10.4103/0250-474X.106063