Synthesis and biological activity of novel mono-indole and mono-benzofuran inhibitors of bacterial transcription initiation complex formation

Marcin Mielczarek, Ruth V. Thomas, Cong Ma, Hakan Kandemir, Xiao Yang, Mohan Bhadbhade, David Stc Black, Renate Griffith, Peter J. Lewis, Naresh Kumar

Research output: Journal article publicationJournal articleAcademic researchpeer-review

24 Citations (Scopus)


Our ongoing research focused on targeting transcription initiation in bacteria has resulted in synthesis of several classes of mono-indole and mono-benzofuran inhibitors that targeted the essential protein-protein interaction between RNA polymerase core and σ70/σAfactors in bacteria. In this study, the reaction of indole-2-, indole-3-, indole-7- and benzofuran-2-glyoxyloyl chlorides with amines and hydrazines afforded a variety of glyoxyloylamides and glyoxyloylhydrazides. Similarly, condensation of 2- and 7-trichloroacetylindoles with amines and hydrazines delivered amides and hydrazides. The novel molecules were found to inhibit the RNA polymerase-σ70/σAinteraction as measured by ELISA, and also inhibited the growth of both Gram-positive and Gram-negative bacteria in culture. Structure-activity relationship (SAR) studies of the mono-indole and mono-benzofuran inhibitors suggested that the hydrophilic-hydrophobic balance is an important determinant of biological activity.
Original languageEnglish
Pages (from-to)1763-1775
Number of pages13
JournalBioorganic and Medicinal Chemistry
Issue number8
Publication statusPublished - 15 Apr 2015
Externally publishedYes


  • Antibacterial activity
  • Mono-benzofurans
  • Mono-indoles
  • r70/rA factors
  • RNA polymerase
  • Structure-activity relationship (SAR)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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