Chemical scaffolds with structural similarities to siderophores of nonribosomal peptide-polyketide origin as novel antimicrobials against Mycobacterium tuberculosis and Yersinia pestis

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:21

Article

Ferreras, Julian A.²  Gupta, Akash³  Amin, Neal D.²  Basu, Arijit¹  Sinha, Barij N.¹  Worgall, Stefan⁴  Jayaprakash, Venkatesan¹  Quadri, Luis E. N.³ 

[1] Birla Inst Technol, Dept Pharmaceut Sci, Ranchi 835215, Bihar, India

[2] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA

[3] CUNY Brooklyn Coll, Dept Biol, Brooklyn, NY 11210 USA

[4] Cornell Univ, Weill Med Coll, Dept Pediat & Genet Med, New York, NY 10021 USA

关键词: Nonribosomal peptide;    Polyketide;    Siderophore;    Mycobacterium tuberculosis;    Yersinia pestis;    Antimicrobial compound;    Pyrazoline;    Hydroxyhydrazine;   

DOI  :  10.1016/j.bmcl.2011.08.052

来源: Elsevier

【 摘 要 】

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. Published by Elsevier Ltd.

【 授权许可】

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