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Title

Computational validation of 3-ammonio-3-(4-oxido-1H-imidazol-1-ium-5-yl) propane-1, 1-bis (olate) as a potent anti-tubercular drug against mt-MetAP

 

Authors

Abhishek Chowdhury1*, Shantanu Sen1, Pradip Dey1, Pankaj Chetia1, Anupam Das Talukdar2, Amitabha Bhattacharjee3 & Manabendra Dutta Choudhury1

 

Affiliation

1Bioinformatics Centre (DBT-BIF), Assam University Silchar, Assam, India-788011; 2Department of Life Science & Bioinformatics, Assam University Silchar, India-788011; 3Department of Microbiology, Assam University Silchar, India-788011

 

Email

abhishek@bioinfoaus.ac.in; *Corresponding author

 

Article Type

Hypothesis

 

Date

Received August 21, 2012; Accepted September 03, 2012; Published September 21, 2012

 

Abstract

The advent of Multi Drug Resistant (MDR) strain of Mycobacterium tuberculosis (TB) necessitated search for new drug targets for the bacterium. It is reported that 3.3% of all new tuberculosis cases had multidrug resistance (MDR-TB) in 2009 and each year, about 0.44 million MDR-TB cases are estimated to emerge and 0.15 million people with MDR-TB die. Keeping such an alarming situation under consideration we wanted to design suitable anti tubercular molecules for new target using computational tools. In the work Methionine aminopeptidase (MetAP) of Mycobacterium tuberculosis was considered as target and three non-toxic phenolic/ketonic compounds were considered as ligands. Docking was done with Flex X and AutoDock 4.2 separately. Ten proven inhibitors of MetAP were collected from literature with their IC50 and were correlated using EasyQSAR to generate QSAR model. Activity of ligands in question was predicted from QSAR. Pharmacophore for each docking was generated using Ligandscout 3.0. Toxicity of the ligands in question was predicted on Mobyle@rpbs portal and Actelion property explorer. Molecular docking with target showed that of all three ligands, 3-ammonio-3-(4-oxido-1H-imidazol-1-ium-5-yl) propane-1, 1-bis (olate) has highest affinity (-37.5096) and lowest IC50 (4.46 ÁM). We therefore, propose that -3-ammonio-3-(4-oxido-1H-imidazol-1-ium-5-yl) propane-1,1-bis(olate) as a potent MetAP inhibitor may be a new anti-tubercular drug particularly in the context of Multi Drug Resistant Tuberculosis (MDR-TB).

 

Keywords

Anti-tubercular drug, MetAP, 3-ammonio-3-(4-oxido-1H-imidazol-1-ium-5-yl) propane-1,1-bis(olate)

 

Citation

Chowdhury et al. Bioinformation 8(18): 875-880 (2012)
 

Edited by

P Kangueane

 

ISSN

0973-2063

 

Publisher

Biomedical Informatics

 

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.