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

Perieteanu, Marina C. and McGee, Leah M.C. and Shaw, Craig D. and MacMillan, Donna S. and Khalaf, Abedawn I. and Gillingwater, Kirsten and Beveridge, Rebecca and Carter, Katharine C. and Suckling, Colin J. and Scott, Fraser J. (2022) Selective anti-Leishmanial Strathclyde minor groove binders using an N-oxide tail group modification. International Journal of Molecular Sciences, 23 (19). 11912. ISSN 1422-0067 (https://doi.org/10.3390/ijms231911912)

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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.

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