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

Austin, Michael J., Hearnshaw, Stephen J., Mitchenall, Lesley A., McDermott, Paul J., Howell, Lesley A., Maxwell, Anthony and Searcey, Mark ORCID: https://orcid.org/0000-0003-2273-8949 (2016) A natural product inspired fragment-based approach towards the development of novel anti-bacterial agents. MedChemComm, 7 (7). pp. 1387-1391. ISSN 2040-2503

Microsoft Word (Searcey MedChemComm SD8 2016) - Accepted Version Download (1MB)

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.

Item Type:	Article
Faculty \ School:	Faculty of Science > School of Pharmacy (former - to 2024) Faculty of Science > School of Chemistry (former - to 2024)
UEA Research Groups:	Faculty of Science > Research Groups > Chemical Biology and Medicinal Chemistry (former - to 2021) Faculty of Science > Research Groups > Innovations in Pharmacy Education (former - to 2025) Faculty of Science > Research Groups > Synthetic and Medicinal Chemistry Faculty of Science > Research Groups > Education Research & Practice
Depositing User:	Pure Connector
Date Deposited:	23 May 2016 16:01
Last Modified:	18 Jun 2026 17:07
URI:	https://ueaeprints.uea.ac.uk/id/eprint/59017
DOI:	10.1039/C6MD00229C

Downloads

Actions (login required)

View Item