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 language | English |
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Pages (from-to) | 3705-3711 |
Journal | Bioorganic & Medicinal Chemistry |
Volume | 23 |
Issue number | 13 |
Early online date | 8 Apr 2015 |
DOIs | |
Publication status | Published - 1 Jul 2015 |
Keywords
- Distamycin
- Antibiotic resistance
- Anti-tubercular agents
- DNA-minor groove ligands
- Whole cell phenotypic evaluation
- Combinatorial chemistry