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

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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
Depositing User:	Pure Connector
Date Deposited:	23 May 2016 16:01
Last Modified:	24 Sep 2024 11:41
URI:	https://ueaeprints.uea.ac.uk/id/eprint/59017
DOI:	10.1039/C6MD00229C

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