Design, synthesis and antibacterial activity of minor groove binders: the role of non-cationic tail groups

Abedawn Khalaf, Claire Bourdin, David Breen, Gavin Donoghue, Fraser Scott, Colin Suckling, Donna MacMillan, Carol Clements, Keith Fox, Doreen Sekibo

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15 Citations (Scopus)
121 Downloads (Pure)


he design and synthesis of a new class of minor groove binder (MGBs) in which, the cationic tail group has been replaced by a neutral, polar variant including cyanoguanidine, nitroalkene, and trifluoroacetamide groups. Antibacterial activity (against Gram positive bacteria) was found for both the nitroalkene and trifluoroacetamide groups. For the case of the nitroalkene tail group, strong binding of a minor groove binder containing this tail group was demonstrated by both DNA footprinting and melting temperature measurements, showing a correlation between DNA binding and antibacterial activity. The compounds have also been evaluated for binding to the hERG ion channel to determine whether non-cationic but polar substituents might have an advantage compared with conventional cationic tail groups in avoiding hERG binding. In this series of compounds, it was found that whilst non-cationic compounds generally had lower affinity to the hERG ion channel, all of the compounds studied bound weakly to the hERG ion channel, probably associated with the hydrophobic head groups.
Original languageEnglish
Pages (from-to)39-47
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Early online date16 Aug 2012
Publication statusPublished - 2012


  • antibacterial activity
  • minor groove binders
  • trifluoroacetamide


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