A natural product inspired fragment-based approach towards the development of novel anti-bacterial agents

Michael J. Austin, Stephen J. Hearnshaw, Lesley A. Mitchenall, Paul J. McDermott, Lesley A. Howell, Anthony Maxwell, Mark Searcey

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)
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The discovery of new antibiotics with novel modes of action to combat antimicrobial resistance (AMR) is of vital importance. The natural product simocyclinone D8 (SD8) is a potent inhibitor of DNA gyrase. Its bi-functional structure and novel mode of action serve as an inspiring lead for antibiotic development. Herein we describe a proof of principle fragment-based approach towards the development of a new class of coumarin-quinolone hybrids. We demonstrate that the coumarin moiety is required for the observed inhibitory activity (IC50 ~3 M) of the hybrid compound, which is in part mediated through stabilisation of a cleaved-DNA intermediate.
Original languageEnglish
Pages (from-to)1387-1391
Number of pages5
Issue number7
Early online date18 May 2016
Publication statusPublished - 1 Jul 2016

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