Synthesis, anti-mycobacterial activity and DNA sequence-selectivity of a library of biaryl-motifs containing polyamides. Issue 13 (1st July 2015)

• Record Type: Journal Article
• Authors: Brucoli, Federico; Guzman, Juan D.; Maitra, Arundhati; James, Colin H.; Fox, Keith R.; Bhakta, Sanjib
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 13(2015)
• Page Start: 3705
• Page End: 3711
• Publication Date: 2015-07-01
• Subjects: Distamycin -- Antibiotic resistance -- Anti-tubercular agents -- DNA-minor groove ligands -- Whole cell phenotypic evaluation -- Combinatorial chemistry; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.04.001
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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-motifs2 ( 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 polyamide2 ( 2, 6 ) exhibited 10-fold higher inhibitory activity against Mycobacterium tuberculosis compared to distamycin and library member2 ( 5, 7 ) showed high binding affinity for the 5′-ACATAT-3′ sequence.