Design, synthesis and structure-activity relationship of novel Relacin analogs as inhibitors of Rel proteins

Ezequiel Wexselblatt, Ilana Kaspy, Gad Glaser, Joshua Katzhendler, Eylon Yavin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Rel proteins in bacteria synthesize the signal molecules (p)ppGpp that trigger the Stringent Response, responsible for bacterial survival. Inhibiting the activity of such enzymes prevents the Stringent Response, resulting in the inactivation of long-term bacterial survival strategies, leading to bacterial cell death. Herein, we describe a series of deoxyguanosine-based analogs of the Relacin molecule that inhibit in vitro the synthetic activity of Rel proteins from Gram positive and Gram negative bacteria, providing a deeper insight on the SAR for a better understanding of their potential interactions and inhibitory activity. Among the inhibitors evaluated, compound 2d was found to be more effective and potent than our previously reported Relacin.

Original languageAmerican English
Pages (from-to)497-504
Number of pages8
JournalEuropean Journal of Medicinal Chemistry
Volume70
DOIs
StatePublished - 2013

Keywords

  • (p)ppGpp
  • Antibacterial
  • Purine
  • RelA
  • Stringent Response

Fingerprint

Dive into the research topics of 'Design, synthesis and structure-activity relationship of novel Relacin analogs as inhibitors of Rel proteins'. Together they form a unique fingerprint.

Cite this