Selective anti-Leishmanial Strathclyde minor groove binders using an N-oxide tail group modification

Marina C. Perieteanu, Leah M.C. McGee, Craig D. Shaw, Donna S. MacMillan, Abedawn I. Khalaf, Kirsten Gillingwater, Rebecca Beveridge, Katharine C. Carter, Colin J. Suckling, Fraser J. Scott

Research output: Contribution to journalArticlepeer-review

3 Downloads (Pure)

Abstract

The neglected tropical disease leishmaniasis, caused by Leishmania spp., is becoming more problematic due to the emergence of drug-resistant strains. Therefore, new drugs to treat leishmaniasis, with novel mechanisms of action, are urgently required. Strathclyde minor groove binders (S-MGBs) are an emerging class of anti-infective agent that have been shown to have potent activity against various bacteria, viruses, fungi and parasites. Herein, it is shown that S-MGBs have potent activity against L. donovani, and that an N-oxide derivation of the tertiary amine tail of typical S-MGBs leads to selective anti-leishmanial activity. Additionally, using S-MGB-219, the N-oxide derivation is shown to retain strong binding to DNA as a 2:1 dimer. These findings support the further study of anti-leishmanial S-MGBs as novel therapeutics.
Original languageEnglish
Article number11912
Number of pages16
JournalInternational Journal of Molecular Sciences
Volume23
Issue number19
Early online date7 Oct 2022
DOIs
Publication statusPublished - 7 Oct 2022

Keywords

  • leishmaniasis
  • minor groove binders
  • S-MGB
  • DNA

Fingerprint

Dive into the research topics of 'Selective anti-Leishmanial Strathclyde minor groove binders using an N-oxide tail group modification'. Together they form a unique fingerprint.

Cite this