Francis, D, Farooque, S, Meager, A et al. (5 more authors) (2022) Algorithm-driven activity-directed expansion of a series of antibacterial quinazolinones. Organic and Biomolecular Chemistry, 20 (48). pp. 9672-9678. ISSN 1477-0520
Abstract
Activity-directed synthesis (ADS) is a structure-blind, function driven approach that can drive the discovery of bioactive small molecules. In ADS, arrays of reactions are designed and executed, and the crude product mixtures are then directly screened to identify reactions that yield bioactive products. The design of subsequent reaction arrays is then informed by the hit reactions that are discovered. In this study, algorithms for reaction array design were developed in which the reactions to be executed were selected from a large set of virtual reactions; the reactions were selected on the basis of similarity to reactions known to yield bioactive products. The algorithms were harnessed to design arrays of photoredox-catalysed alkylation reactions whose crude products were then screened for inhibition of growth of S. aureus ATCC29213. It was demonstrated that the approach enabled expansion of a series of antibacterial quinazolinones. It is envisaged that such algorithms could ultimately enable fully autonomous activity-directed molecular discovery.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Royal Society of Chemistry 2022. This is an open access an articleunder the terms of the Creative Commons Attribution 3.0 Unported (CC BY 3.0) |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Organic Chemistry (Leeds) The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Physical Chemistry (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Funding Information: | Funder Grant number EPSRC (Engineering and Physical Sciences Research Council) EP/N025652/1 |
Depositing User: | Symplectic Publications |
Date Deposited: | 13 Dec 2022 16:39 |
Last Modified: | 27 Jun 2023 14:18 |
Status: | Published |
Publisher: | Royal Society of Chemistry |
Identification Number: | 10.1039/d2ob01404a |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:193950 |
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