Design, synthesis and antibacterial activity of minor groove binders: the role of non-cationic tail groups
Khalaf, Abedawn and Bourdin, Claire and Breen, David and Donoghue, Gavin and Scott, Fraser and Suckling, Colin and MacMillan, Donna and Clements, Carol and Fox, Keith and Sekibo, Doreen (2012) Design, synthesis and antibacterial activity of minor groove binders: the role of non-cationic tail groups. European Journal of Medicinal Chemistry, 56. pp. 39-47. ISSN 0223-5234 (https://doi.org/10.1016/j.ejmech.2012.08.013.)
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Abstract
he design and synthesis of a new class of minor groove binder (MGBs) in which, the cationic tail group has been replaced by a neutral, polar variant including cyanoguanidine, nitroalkene, and trifluoroacetamide groups.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.
ORCID iDs
Khalaf, Abedawn ORCID: https://orcid.org/0000-0001-9162-7527, Bourdin, Claire, Breen, David ORCID: https://orcid.org/0000-0002-9341-5744, Donoghue, Gavin, Scott, Fraser ORCID: https://orcid.org/0000-0003-0229-3698, Suckling, Colin, MacMillan, Donna, Clements, Carol, Fox, Keith and Sekibo, Doreen;-
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Item type: Article ID code: 40853 Dates: DateEvent2012Published16 August 2012Published OnlineSubjects: Science > Chemistry Department: Faculty of Science > Pure and Applied Chemistry
Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical SciencesDepositing user: Pure Administrator Date deposited: 10 Aug 2012 08:46 Last modified: 02 Oct 2024 00:22 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/40853