Synthesis, anti-mycobacterial activity and DNA sequence-selectivity of a library of biaryl-motifs containing polyamides

Federico Brucoli, Juan D. Guzman, Arundhati Maitra, Colin H. James, Keith R. Fox, Sanjib Bhakta

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

The alarming rise of extensively drug-resistant tuberculosis (XDR-TB) strains, compel the development of new molecules with novel modes of action to control this world health emergency. Distamycin analogues containing N-terminal biaryl-motifs 2(1-5)(1-7) were synthesised using a solution-phase approach and evaluated for their anti-mycobacterial activity and DNA-sequence selectivity. Thiophene dimer motif-containing polyamide 2(2,6) exhibited 10-fold higher inhibitory activity against Mycobacterium tuberculosis compared to distamycin and library member 2(5,7) showed high binding affinity for the 5'-ACATAT-3' sequence.
Original languageEnglish
Pages (from-to)3705-3711
JournalBioorganic & Medicinal Chemistry
Volume23
Issue number13
Early online date8 Apr 2015
DOIs
Publication statusPublished - 1 Jul 2015

Keywords

  • Distamycin
  • Antibiotic resistance
  • Anti-tubercular agents
  • DNA-minor groove ligands
  • Whole cell phenotypic evaluation
  • Combinatorial chemistry

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