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

9 Citations (Scopus)
21 Downloads (Pure)

Abstract

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
JournalMedChemComm
Volume7
Issue number7
Early online date18 May 2016
DOIs
Publication statusPublished - 1 Jul 2016

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