Design, Synthesis and Microbiological Evaluation of Novel Compounds as Potential Staphylococcus aureus Phenylalanine tRNA Synthetase Inhibitors

Document Type : Original Article

Authors

1 School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK

2 Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig P.C. 44519, Egypt

3 Department of Chemistry, University of Texas – Rio Grande Valley, 1201 W. University Drive, Edinburg, TX 78541, USA

4 Specialist Antimicrobial Chemotherapy Unit, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, UK

5 School of Molecular & Cellular Biology, Garstang Building, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK

Abstract

As the resistance of Staphylococcus aureus to antibiotics represents a major threat to global health, anti-infectives with novel mechanisms must be developed. Novel compounds were generated as potential phenylalanine tRNA synthetase (PheRS) inhibitors based on the published homology model of S. aureus PheRS to aid the design process using Molecular Operating Environment (MOE) software. PheRS was selected as it is structurally unique enzyme among the aminoacyl-tRNA syntheases (aaRS), it is considerably different from human cytosolic and human mitochondrial aaRS and it is essential and conserved across bacterial species. The designed compounds were synthesized according to different clear schemes. The compounds were confirmed by 1H NMR, 13C NMR, HRMS and/or microanalysis, and they were microbiologically evaluated.

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History

  • Receive Date: 12 June 2018
  • Revise Date: 23 June 2018
  • Accept Date: 10 July 2018

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