The discovery of new antibiotics with novel modes of action to combat antimicrobial resistance (AMR) is ofvital importance. The natural product simocyclinone D8 (SD8) is a potent inhibitor of DNA gyrase. Its bifunctionalstructure and novel mode of action serve as an inspiring lead for antibiotic development. Hereinwe describe a proof of principle fragment-based approach towards the development of a new class ofcoumarin-quinolone hybrids. We demonstrate that the coumarin moiety is required for the observed inhibitoryactivity (IC50 ∼ 3 μM) of the hybrid compound, which is in part mediated through stabilisation of acleaved-DNA intermediate.