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

Marcins Mielczarek, Ruth V. Devakaram, Cong Ma, Xiao Yang, Hakan Kandemir, Bambang Purwono, David Stc Black, Renate Griffith, Peter J. Lewis, Naresh Kumar

Research output: Journal article publicationJournal articleAcademic researchpeer-review

28 Citations (Scopus)


The increasing resistance of bacteria against clinically approved antibiotics is resulting in an alarming decrease in therapeutic options for today's clinicians. We have targeted the essential interaction between bacterial RNA polymerase and σ70/σA for the development of lead molecules exhibiting a novel mechanism of antibacterial activity. Several classes of structurally related bis-indole inhibitors of bacterial transcription initiation complex formation were synthesized and their antimicrobial activities were evaluated. Condensation of indole-7- and indole-2-carbohydrazides with 7- and 2-trichloroacetylindoles or indole-7- and indole-2-glyoxyloyl chlorides resulted in the successful synthesis of 7,7′-, 2,2′-, 2,7′- and 3,2′-linked bis-indole derivatives with -CO-NH-NH-CO- and -CO-CO-NH-NH-CO- linkers. Indole-7-glyoxyloyl chlorides were reacted with hydrazine hydrate in different ratios to afford respective -CO-CO-NH-NH-CO-CO- bis-indole or hydrazide derivatives. The resulting compounds were found to be active against the β′-CH- σ70/σA2.2 interaction in ELISA assays and inhibited the growth of both Gram-positive and Gram-negative bacteria. Structure-activity relationship (SAR) studies were performed in order to identify the structural features of the synthesized inhibitors required for biological activity. This journal is
Original languageEnglish
Pages (from-to)2882-2894
Number of pages13
JournalOrganic and Biomolecular Chemistry
Issue number18
Publication statusPublished - 14 May 2014
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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