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.
|Number of pages||5|
|Early online date||18 May 2016|
|Publication status||Published - 1 Jul 2016|
- School of Pharmacy - Pro-Vice-Chancellor
- Norwich Institute for Healthy Aging - Member
Person: Research Centre Member, Academic, Teaching & Research