Distamycin Analogues with Enhanced Lipophilicity: Synthesis and Antimicrobial Activity

A.I. Khalaf, R.D. Waigh, A.J. Drummond, B. Pringle, I. McGroarty, G.G. Skellern, C.J. Suckling

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Forty-eight heterocyclic amino acid trimers, analogues of distamycin, with a number of features that enhance lipophilicity are described. They contain alkyl or cycloalkyl groups larger than methyl; some are N-terminated by acetamide or methoxybenzamide and are C-terminated by dimethylaminopropyl or aliphatic heterocylic aminopropyl substituents. The ability of these compounds to bind principally to AT tracts of DNA has been evaluated using capillary zone electrophoresis. Significant antimicrobial activity against key organisms such as MRSA and Candida albicans is shown by several compounds, especially those containing a thiazole. Moreover, these compounds have low toxicity with respect to several mammalian cell lines.
LanguageEnglish
Pages2133-2156
Number of pages23
JournalJournal of Medicinal Chemistry
Volume47
Issue number8
DOIs
Publication statusPublished - 5 Mar 2004

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Heterocyclic Acids
Thiazoles
Capillary Electrophoresis
Methicillin-Resistant Staphylococcus aureus
Candida albicans
Amino Acids
Cell Line
DNA
acetamide
stallimycin

Keywords

  • distamycin analogues
  • antimicrobial activity
  • heterocyclic amino acid trimers
  • methoxybenzamide
  • dimethylaminopropyl
  • applied chemistry
  • pure chemistry
  • pure and applied chemistry

Cite this

Khalaf, A. I., Waigh, R. D., Drummond, A. J., Pringle, B., McGroarty, I., Skellern, G. G., & Suckling, C. J. (2004). Distamycin Analogues with Enhanced Lipophilicity: Synthesis and Antimicrobial Activity. Journal of Medicinal Chemistry, 47(8), 2133-2156. https://doi.org/10.1021/jm031089x
Khalaf, A.I. ; Waigh, R.D. ; Drummond, A.J. ; Pringle, B. ; McGroarty, I. ; Skellern, G.G. ; Suckling, C.J. / Distamycin Analogues with Enhanced Lipophilicity: Synthesis and Antimicrobial Activity. In: Journal of Medicinal Chemistry. 2004 ; Vol. 47, No. 8. pp. 2133-2156.
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Khalaf, AI, Waigh, RD, Drummond, AJ, Pringle, B, McGroarty, I, Skellern, GG & Suckling, CJ 2004, 'Distamycin Analogues with Enhanced Lipophilicity: Synthesis and Antimicrobial Activity' Journal of Medicinal Chemistry, vol. 47, no. 8, pp. 2133-2156. https://doi.org/10.1021/jm031089x

Distamycin Analogues with Enhanced Lipophilicity: Synthesis and Antimicrobial Activity. / Khalaf, A.I.; Waigh, R.D.; Drummond, A.J.; Pringle, B.; McGroarty, I.; Skellern, G.G.; Suckling, C.J.

In: Journal of Medicinal Chemistry, Vol. 47, No. 8, 05.03.2004, p. 2133-2156.

Research output: Contribution to journalArticle

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Khalaf AI, Waigh RD, Drummond AJ, Pringle B, McGroarty I, Skellern GG et al. Distamycin Analogues with Enhanced Lipophilicity: Synthesis and Antimicrobial Activity. Journal of Medicinal Chemistry. 2004 Mar 5;47(8):2133-2156. https://doi.org/10.1021/jm031089x