One way to search for the target is to select for resistant mutants, then sequence the genomes of the parent and mutant strains and look for changes. Sometimes, the change will be in the target, but not always. The resistant mutant strain can then be selected for even greater resistance in a second step, and the new mutant sequenced. Sometimes, this will result in target mutations when the lesser resistance does not.

To confirm the target, it will be desirable to demonstrate binding of the compound to the target, or to show that the function of the putative target is impaired in cells treated with the compound. Additional supportive experiments include overexpressing the target to bring about resistance, or attenuating expression to cause sensitization to the compound.

Dear Vasantha,

I suggest that you read the following publications that might give you a clear picture on the molecular target for your antibacterial agent. The first two publications are review articles that cover the molecular targets for all known natural antibacterials.

1-Bioorganic & Medicinal Chemistry Letters

Volume 24, Issue 2, 15 January 2014, Pages 413–418

BMCL Digest

New natural products as new leads for antibacterial drug discovery

Dean G. Brown, ,

Troy Lister,

Tricia L. May-Dracka

Abstract

Natural products have been a rich source of antibacterial drugs for many decades, but investments in this area have declined over the past two decades. The purpose of this review article is to provide a recent survey of new natural product classes and the mechanisms by which they work.

Graphical abstract

Natural products have been a rich source of antibacterial drugs for many decades, but investments in this area have declined over the past two decades. The purpose of this review article is to provide a recent survey of new natural product classes and the mechanisms by which they work.

http://www.sciencedirect.com/science/article/pii/S0960894X13014315

2-Metabolites. 2012 Jun; 2(2): 303–336.

Published online 2012 Apr 16. doi:  10.3390/metabo2020303

PMCID: PMC3901206

A Historical Overview of Natural Products in Drug Discovery

Daniel A. Dias,1,* Sylvia Urban,2 and Ute Roessner1,3

Author information ► Article notes ► Copyright and License information ►

This article has been cited by other articles in PMC.

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Abstract

Historically, natural products have been used since ancient times and in folklore for the treatment of many diseases and illnesses. Classical natural product chemistry methodologies enabled a vast array of bioactive secondary metabolites from terrestrial and marine sources to be discovered. Many of these natural products have gone on to become current drug candidates. This brief review aims to highlight historically significant bioactive marine and terrestrial natural products, their use in folklore and dereplication techniques to rapidly facilitate their discovery. Furthermore a discussion of how natural product chemistry has resulted in the identification of many drug candidates; the application of advanced hyphenated spectroscopic techniques to aid in their discovery, the future of natural product chemistry and finally adopting metabolomic profiling and dereplication approaches for the comprehensive study of natural product extracts will be discussed.

Keywords: natural products, secondary metabolites, drug discovery, bioactivity, metabolomics, dereplication, plants, sponges, algae, fungi

To view the full publication, please see attached file.

3- Open Journal of Genomics

ISSN: 2075-9061

Volume 3, 2014

Identifying antibacterial targets of flavonoids by comparative genomics and molecular modeling

Zheng-Tao Xiao, Qiang Zhu, Hong-Yu Zhang*

Center for Bioinformatics, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China

DOI: 10.13055/ojgen_3_1_1.140317

  Corresponding Address:

* Center for Bioinformatics, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China; Fax: +86 27 87280877; Email: [email protected]

ABSTRACT

Flavonoids are among most common natural products that exhibit a broad spectrum of antibacterial activity. In order to decipher their antibacterial mechanisms, we used comparative genomics method to identify the targets in E. coli for 19 antibacterial flavonoids, and then validated these targets by molecular docking. Five important enzymes, namely, fumarate reductase flavoprotein, dihydroorotate dehydrogenase, dihydrofolate reductase, NADH-dependent enoyl-ACP reductase, and the DNA gyrase subunit, were identified as potential targets of 19 flavonoids. Docking results also showed that the 3-O-galloyl or 3-O-glycosides side chain at flavonoid pyrane ring are important for inhibiting these enzymes. This study not only provides important clues to understanding antibacterial mechanisms of flavonoids, but also demonstrates that comparative genomics is useful in predicting natural product targets.

Keywords: antibacterial targets, comparative genomics, flavonoids, molecular modeling.

http://rossscience.org/ARTICLE/OJGEN-3-1.php

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The re-emergence of natural products for drug discovery in the genomics era

Alan L. Harvey,

RuAngelie Edrada-Ebel

& Ronald J. Quinn

Affiliations

Corresponding author

Nature Reviews Drug Discovery

14,

111–129

(2015)

doi:10.1038/nrd4510

Published online

23 January 2015

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Abstract

Abstract•

References•

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Natural products have been a rich source of compounds for drug discovery. However, their use has diminished in the past two decades, in part because of technical barriers to screening natural products in high-throughput assays against molecular targets. Here, we review strategies for natural product screening that harness the recent technical advances that have reduced these barriers. We also assess the use of genomic and metabolomic approaches to augment traditional methods of studying natural products, and highlight recent examples of natural products in antimicrobial drug discovery and as inhibitors of protein–protein interactions. The growing appreciation of functional assays and phenotypic screens may further contribute to a revival of interest in natural products for drug discovery.

http://www.nature.com/nrd/journal/v14/n2/full/nrd4510.html

I suggest that you join CO-ADD (Community for Open Antimicrobial Drug Discovery)

http://www.co-add.org/content/info-submission-campaign?gclid=Cj0KEQiAz5y1BRDZ4Z_K_eGa84cBEiQAtQkeaBZfc1iTdRAC8T5hn4J8T2l8sULklPFdpK5M0fZg5p4aAuok8P8HAQ

SENDING COMPOUNDS

Do you have the next antibiotic?

CO-ADD offers free primary screening of 5 key ESKAPE pathogens (E. coli, MRSA, Klebsellia pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa) and 2 fungi (Cryptococcus neoformans and Candida albicans). We only need 1mg of compound and you do not need to provide a structure.

WHAT IS CO-ADD?

The Community for Open Antimicrobial Drug Discovery (CO-ADD) is a global, not-for-profit, open-access research program reaching out to academic chemists who have compounds ‘sitting on shelves’that were not designed as antibiotics and would not otherwise be screened for antimicrobial activity. These compounds are screened at no cost against a key panel of drug-resistant bacterial and fungal strains in our laboratories located at The University of Queensland's Institute for Molecular Bioscience.

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Compound libraries are screened free of charge against a key panel of susceptible and drug-resistant bacterial, and fungal pathogens. All molecules will go through primary screening to provide initial activity data, active compounds will be taken through hit confirmation and cytotoxicity assays, and lead compounds will be tested against a broader panel of microbes and initial ADMET screening for hit validation.

In sending compounds to CO-ADD you accept our terms and conditions.

Hoping this will be helpful,

Rafik

One way to search for the target is to select for resistant mutants, then sequence the genomes of the parent and mutant strains and look for changes. Sometimes, the change will be in the target, but not always. The resistant mutant strain can then be selected for even greater resistance in a second step, and the new mutant sequenced. Sometimes, this will result in target mutations when the lesser resistance does not.

To confirm the target, it will be desirable to demonstrate binding of the compound to the target, or to show that the function of the putative target is impaired in cells treated with the compound. Additional supportive experiments include overexpressing the target to bring about resistance, or attenuating expression to cause sensitization to the compound.

Bioinformatics would be suitable, prima facie, for the targeted bacterium. For different types of bacteria different targets are being worked out..