Truncated S-MGBs: towards a parasite-specific and low aggregation chemotype

Daniel P. Brooke, Leah M. C. McGee, Federica Giordani, Jasmine M. Cross, Abedawn I. Khalaf, Craig Irving, Kirsten Gillingwater, Craig D. Shaw, Katharine C. Carter, Michael P. Barrett, Colin J. Suckling, Fraser J. Scott

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Abstract

This paper describes the design and synthesis of Strathclyde minor groove binders (S-MGBs) that have been truncated by the removal of a pyrrole ring in order to mimic the structure of the natural product, disgocidine. S-MGBs have been found to be active against many different organisms, however, selective antiparasitic activity is required. A panel of seven truncated S-MGBs was prepared and the activities examined against a number of clinically relevant organisms including several bacteria and parasites. The effect of the truncation strategy on S-MGB aggregation in aqueous environment was also investigated using 1H inspection and DOSY experiments. A lead compound, a truncated S-MGB, which possesses significant activity only against trypanosomes and Leishmania has been identified for further study and was also found to be less affected by aggregation compared to its full-length analogue.
Original languageEnglish
Pages (from-to)1391-1401
Number of pages11
JournalRSC Medicinal Chemistry
Volume12
Issue number8
Early online date6 Jul 2021
DOIs
Publication statusPublished - Aug 2021

Keywords

  • Strathclyde minor groove binders
  • disgocidine
  • parasites
  • bacteria

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