BACK TO CONTENTS   |    PDF   |    PREVIOUS   |    NEXT

Title

Molecular docking of azole drugs and their analogs on CYP121 of Mycobacterium tuberculosis

 

Authors

Jagadish Chandrabose Sundaramurthi, Swetha Kumar, Kannayan Silambuchelvi, Luke Elizabeth Hanna*

 

Affiliation

ICMR-Biomedical Informatics Centre, Tuberculosis Research Centre, (ICMR), Chetpet, Chennai-600031, Tamil Nadu, India

 

Email

hannatrc@yahoo.com; *Corresponding author

 

Article Type

Hypothesis

 

Date

Received August 27, 2011; Accepted August 30, 2011; Published September 28, 2011

 

Abstract

The Mycobacterium tuberculosis genome codes for 20 different cytochromes. These cytochromes are involved in the breakdown of recalcitrant pollutants and the synthesis of polyketide antibiotics and other complex macromolecules. It has been demonstrated that CYP121 is essential for viability of the bacterium by gene knock-out and complementation studies. CYP121 could therefore be a probable target for the development of new drugs for TB. It has been widely reported that orthologs of CYP121 in fungi are inhibited by azole drugs. We evaluated whether these azole drugs or their structural analogs could bind to and inhibit CYP121 of M. tuberculosis using molecular docking. Six molecules with known anti-CYP121 activity were selected from literature and PubChem database was searched to identify structural analogs for these inhibitors. Three hundred and fifty seven molecules were identified as structural analogs and used in docking studies. Fifty three molecules were found to be scored better than the azole drugs and five of them were ranked among the top 12 molecules by two different scoring functions. These molecules may be further tested by in vitro experimentation for their activity against CYP121 of M. tuberculosis.

 

Keywords

CYP121, M. tuberculosis, docking, ketoconazole, azole drugs.

 

Citation

Sundaramurthi et al. Bioinformation 7(3): 130-133 (2011)
 

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.