Hexadentate 3-hydroxypyridin-4-ones with high iron(III) affinity: design, synthesis and inhibition on methicillin resistant Staphylococcus aureus and Pseudomonas strains

Ying-Jun Zhou; Mu-Song Liu; Al Rugaie Osamah; Xiao-Le Kong; Selwa Alsam; Sinan Battah; Yuan-Yuan Xie; Robert C Hider; Tao Zhou

doi:10.1016/j.ejmech.2015.02.050

Hexadentate 3-hydroxypyridin-4-ones with high iron(III) affinity: design, synthesis and inhibition on methicillin resistant Staphylococcus aureus and Pseudomonas strains

Eur J Med Chem. 2015 Apr 13:94:8-21. doi: 10.1016/j.ejmech.2015.02.050. Epub 2015 Feb 26.

Authors

Ying-Jun Zhou¹, Mu-Song Liu², Al Rugaie Osamah³, Xiao-Le Kong⁴, Selwa Alsam³, Sinan Battah³, Yuan-Yuan Xie², Robert C Hider⁴, Tao Zhou⁵

Affiliations

¹ School of Food Science and Biotechnology, Zhejiang Gongshang University, 18 Xuezheng Street, Xiasha, Hangzhou, Zhejiang, 310018, PR China.
² College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, 310014, PR China.
³ School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK.
⁴ Division of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
⁵ School of Food Science and Biotechnology, Zhejiang Gongshang University, 18 Xuezheng Street, Xiasha, Hangzhou, Zhejiang, 310018, PR China. Electronic address: taozhou@zjgsu.edu.cn.

PMID: 25747496
DOI: 10.1016/j.ejmech.2015.02.050

Abstract

A range of hexadentate 3-hydroxypyridin-4-ones have been synthesized. These compounds were found to possess a high affinity for iron(III), with logK1 values of about 34 and pFe values over 30. Antimicrobial assays indicated that they can inhibit the growth of three clinical isolates of methicillin resistant Staphylococcus aureus (MRSA) and three clinical isolates of Pseudomonas, suggesting that hexadentate 3-hydroxypyridin-4-ones have potential application in the treatment of wound infections.

Keywords: Antimicrobial activity; Hexadentate; Hydroxypyridinone; Iron chelator; MRSA; Pseudomonas aeruginosa.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry*
Anti-Bacterial Agents / pharmacology*
Chemistry Techniques, Synthetic
Drug Design
Drug Evaluation, Preclinical / methods
Iron / chemistry
Iron Chelating Agents / chemistry
Iron Chelating Agents / pharmacology
Methicillin-Resistant Staphylococcus aureus / drug effects*
Microbial Sensitivity Tests
Pseudomonas aeruginosa / drug effects*
Pyridines / chemistry*
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Iron Chelating Agents
Pyridines
hexadentate 3-hydroxypyridin-4-one
Iron