Chemical Scaffolds with Structural Similarities to Siderophores of Nonribosomal Peptide-polyketide Origin As Novel Antimicrobials Against Mycobacterium Tuberculosis and Yersinia Pestis

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2011 Sep 24

PMID 21940166

Citations 8

Authors

Julian A Ferreras

Akash Gupta

Neal D Amin

Arijit Basu

Barij N Sinha

Stefan Worgall

Venkatesan Jayaprakash

Luis E N Quadri

Affiliations

Soon will be listed here.

Abstract

Mycobacterium tuberculosis (Mtb) and Yersinia pestis (Yp) produce siderophores with scaffolds of nonribosomal peptide-polyketide origin. Compounds with structural similarities to these siderophores were synthesized and evaluated as antimicrobials against Mtb and Yp under iron-limiting conditions mimicking the iron scarcity these pathogens encounter in the host and under standard iron-rich conditions. Several new antimicrobials were identified, including some with increased potency in the iron-limiting condition. Our study illustrates the possibility of screening compound libraries in both iron-rich and iron-limiting conditions to identify antimicrobials that may selectively target iron scarcity-adapted bacteria and highlights the usefulness of building combinatorial libraries of compounds having scaffolds with structural similarities to siderophores to feed into antimicrobial screening programs.

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