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

Brooke, Daniel P. and McGee, Leah M. C. and Giordani, Federica and Cross, Jasmine M. and Khalaf, Abedawn I. and Irving, Craig and Gillingwater, Kirsten and Shaw, Craig D. and Carter, Katharine C. and Barrett, Michael P. and Suckling, Colin J. and Scott, Fraser J. (2021) Truncated S-MGBs : towards a parasite-specific and low aggregation chemotype. RSC Medicinal Chemistry, 12 (8). pp. 1391-1401. ISSN 2040-2511 (https://doi.org/10.1039/D1MD00110H)

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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.

ORCID iDs

Brooke, Daniel P. ORCID logoORCID: https://orcid.org/0000-0002-3688-3330, McGee, Leah M. C. ORCID logoORCID: https://orcid.org/0000-0002-9896-0450, Giordani, Federica, Cross, Jasmine M., Khalaf, Abedawn I., Irving, Craig, Gillingwater, Kirsten, Shaw, Craig D., Carter, Katharine C., Barrett, Michael P., Suckling, Colin J. and Scott, Fraser J. ORCID logoORCID: https://orcid.org/0000-0003-0229-3698;
CORE (COnnecting REpositories)