Volume 4 Supplement 1

Antimicrobial Resistance and Infection Control: Abstracts from the 3rd International Conference on Prevention and Infection Control (ICPIC 2015)

Open Access

Structure-based optimization and discovery of novel 1,3,5-triazine derivatives as bacterial translation inhibitor with favourable metabolic fate

  • UP Singh1,
  • JK Srivastava1 and
  • HR Bhat1
Antimicrobial Resistance and Infection Control20154(Suppl 1):I2

DOI: 10.1186/2047-2994-4-S1-I2

Published: 16 June 2015

Introduction

We have recently moved into an era not just of multiple resistant bacteria but of totally resistant pathogens, which now include vancomycin-resistant enterococci, carbapenem-resistant Acinetobacter baumannii, vancomycin-resistant MRSA and, very recently, NDM-1. Thus, increased incidence of bacterial resistance to currently available antibiotics necessitates the discovery and introduction of new and effective drugs. In our earlier studies, we have discovered a potent antibacterial lead molecule from 1,3,5-triazine (first generation) and its subsequent optimization till its tenth generation results much more advanced analogue with enhanced activity and less toxicity [1].

Objectives

Present study deals with the advancement of novel derivatives of 1,3,5-triazines to increase its efficacy and potency to make them viable drug candidate (eleventh generation).

Methods

The synthesis of analogues was achieved by means of SNAr reaction utilizing distinguished amines. These molecules were then subjected to antibacterial screening against pathogenic Gram-positive and Gram-negative micro-organisms. MetaPrint2D-React from University of Cambridge, UK was utilized for the prediction of metabolites of the compounds.

Results

Entire set of derivatives demonstrated excellent antibacterial activity (1.56 - 25 µg ml-1), and in some instance found equipotent to cefixime as standard. The molecular docking study on eubacterial ribosomal decoding A site (Escherichia coli 16S rRNA A site) confirmed the stability of target compounds into the inner groove of active site by making close H-bonds with highly conserved residues, e.g. Ade38, Gua37, Ade39, and Gua40. Moreover, the most active compound 7e, in MetaPrint2D-React study was not found to be deactivated by human metabolic process, which conform the utility of designed molecules.

Conclusion

We have discovered an another novel 1,3,5-triazine analogs as potent antibacterial agent through structure-based optimization of our defined lead.

Disclosure of interest

None declared.

Authors’ Affiliations

(1)
Department of Pharmaceutical Sciences, Sam Higginbottom Institute of Agriculture, Technology & Sciences

References

  1. Singh B, Bhat HR, Kumawat MK, Singh UP: Structure-guided discovery of 1,3,5-triazine-pyrazole conjugates as antibacterial and antibiofilm agents against pathogens causing human diseases with favourable metabolic fate. Bioorganic & Medicinal Chemistry Letters. 2014, 24: 3321-3325. 10.1016/j.bmcl.2014.05.103.View ArticleGoogle Scholar

Copyright

© Singh et al; licensee BioMed Central Ltd. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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