Activity-directed expansion of a series of antibacterial agents

Abbie Leggott; Justin E. Clarke; Shiao Chow; Stuart L. Warriner; Alex J. O'Neill; Adam Nelson

doi:10.1039/D0CC02361B

Activity-directed expansion of a series of antibacterial agents

Abbie Leggott, Justin E. Clarke, Shiao Chow, Stuart L. Warriner, Alex J. O'Neill^*, Adam Nelson^*

^*Corresponding author for this work

Pure And Applied Chemistry

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

1 Downloads (Pure)

Abstract

The feasibility of using activity-directed synthesis to drive antibacterial discovery was investigated. An array of 220 Pd-catalysed microscale reactions was executed, and the crude product mixtures were evaluated for activity against Staphylococcus aureus. Scale-up of the hit reactions, purification and evaluation, enabled expansion of a class of antibacterial quinazolinones. The novel antibacterials had MICs from 0.016 μg mL⁻¹ (i.e. 38 nM) to 2–4 μg mL⁻¹against S. aureus ATCC29213.

Original language	English
Pages (from-to)	8047-8050
Number of pages	4
Journal	Chemical Communications
Volume	56
Issue number	58
Early online date	15 Jun 2020
DOIs	https://doi.org/10.1039/D0CC02361B
Publication status	Published - 25 Jul 2020

Funding

We thank EPSRC (EP/N025652/1) for funding.

Keywords

activity-directed synthesis
antibacterial discovery
Staphylococcus aureus
antibacterial quinazolinones

Access to Document

10.1039/D0CC02361BLicence: CC BY 3.0

Leggott-etal-CC-2020-Activity-directed-expansion-of-a-series-of-antibacterial-agentsFinal published version, 2.34 MBLicence: CC BY 3.0

Cite this

@article{3e55919b35d348868c0908c0ee73710e,

title = "Activity-directed expansion of a series of antibacterial agents",

abstract = "The feasibility of using activity-directed synthesis to drive antibacterial discovery was investigated. An array of 220 Pd-catalysed microscale reactions was executed, and the crude product mixtures were evaluated for activity against Staphylococcus aureus. Scale-up of the hit reactions, purification and evaluation, enabled expansion of a class of antibacterial quinazolinones. The novel antibacterials had MICs from 0.016 μg mL−1 (i.e. 38 nM) to 2–4 μg mL−1 against S. aureus ATCC29213.",

keywords = "activity-directed synthesis, antibacterial discovery, Staphylococcus aureus, antibacterial quinazolinones",

author = "Abbie Leggott and Clarke, {Justin E.} and Shiao Chow and Warriner, {Stuart L.} and O'Neill, {Alex J.} and Adam Nelson",

year = "2020",

month = jul,

day = "25",

doi = "10.1039/D0CC02361B",

language = "English",

volume = "56",

pages = "8047--8050",

journal = "Chemical Communications",

issn = "1359-7345",

publisher = "Royal Society of Chemistry",

number = "58",

}

TY - JOUR

T1 - Activity-directed expansion of a series of antibacterial agents

AU - Leggott, Abbie

AU - Clarke, Justin E.

AU - Chow, Shiao

AU - Warriner, Stuart L.

AU - O'Neill, Alex J.

AU - Nelson, Adam

PY - 2020/7/25

Y1 - 2020/7/25

N2 - The feasibility of using activity-directed synthesis to drive antibacterial discovery was investigated. An array of 220 Pd-catalysed microscale reactions was executed, and the crude product mixtures were evaluated for activity against Staphylococcus aureus. Scale-up of the hit reactions, purification and evaluation, enabled expansion of a class of antibacterial quinazolinones. The novel antibacterials had MICs from 0.016 μg mL−1 (i.e. 38 nM) to 2–4 μg mL−1 against S. aureus ATCC29213.

AB - The feasibility of using activity-directed synthesis to drive antibacterial discovery was investigated. An array of 220 Pd-catalysed microscale reactions was executed, and the crude product mixtures were evaluated for activity against Staphylococcus aureus. Scale-up of the hit reactions, purification and evaluation, enabled expansion of a class of antibacterial quinazolinones. The novel antibacterials had MICs from 0.016 μg mL−1 (i.e. 38 nM) to 2–4 μg mL−1 against S. aureus ATCC29213.

KW - activity-directed synthesis

KW - antibacterial discovery

KW - Staphylococcus aureus

KW - antibacterial quinazolinones

U2 - 10.1039/D0CC02361B

DO - 10.1039/D0CC02361B

M3 - Article

SN - 1359-7345

VL - 56

SP - 8047

EP - 8050

JO - Chemical Communications

JF - Chemical Communications

IS - 58

ER -

Activity-directed expansion of a series of antibacterial agents

Abstract

Funding

Keywords

Access to Document

Fingerprint

Cite this