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

doi:10.1016/j.bmc.2015.04.001

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

School of Health and Life Sciences

Research output: Contribution to journal › Article › peer-review

10 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 language	English
Pages (from-to)	3705-3711
Journal	Bioorganic & Medicinal Chemistry
Volume	23
Issue number	13
Early online date	8 Apr 2015
DOIs	https://doi.org/10.1016/j.bmc.2015.04.001
Publication status	Published - 1 Jul 2015

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmc.2015.04.001

Cite this

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

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.",

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T1 - Synthesis, anti-mycobacterial activity and DNA sequence-selectivity of a library of biaryl-motifs containing polyamides

AU - Brucoli, Federico

AU - Guzman, Juan D.

AU - Maitra, Arundhati

AU - James, Colin H.

AU - Fox, Keith R.

AU - Bhakta, Sanjib

N1 - 12 months embargo

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AB - 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.

KW - Distamycin

KW - Antibiotic resistance

KW - Anti-tubercular agents

KW - DNA-minor groove ligands

KW - Whole cell phenotypic evaluation

KW - Combinatorial chemistry

U2 - 10.1016/j.bmc.2015.04.001

DO - 10.1016/j.bmc.2015.04.001

M3 - Article

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JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

SN - 0968-0896

IS - 13

ER -

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

Abstract

Keywords

UN SDGs

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