2. Academic Validation
  3. Synthesis, anti-mycobacterial activity and DNA sequence-selectivity of a library of biaryl-motifs containing polyamides

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

  • Bioorg Med Chem. 2015 Jul 1;23(13):3705-11. doi: 10.1016/j.bmc.2015.04.001.
Federico Brucoli 1,  Juan D Guzman 2,  Arundhati Maitra 2,  Colin H James 3,  Keith R Fox 4,  Sanjib Bhakta 2
Affiliations

Affiliations

  • 1 School of Science and Sport, Institute of Biomedical and Environmental Health Research (IBEHR), University of the West of Scotland, Paisley PA1 2BE, UK. Electronic address: [email protected].
  • 2 Mycobacteria Research Laboratory, Department of Biological Sciences, The Institute of Structural and Molecular Biology, Birkbeck, University of London, London WC1E 7HX, UK.
  • 3 UCL School of Pharmacy, London, 29-39 Brunswick Square, London WC1N 1AX, UK.
  • 4 Centre for Biological Sciences, Life Sciences Building 85, University of Southampton, Southampton SO17 1BJ, UK.
PMID: 25921267 DOI: 10.1016/j.bmc.2015.04.001
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.

Keywords

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

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