Wilkinson, C., McPhillie, M.J., Zhou, Y. et al. (10 more authors) (2014) The benzimidazole based drugs show good activity against T. gondii but poor activity against its proposed enoyl reductase enzyme target. Bioorganic & Medicinal Chemistry Letters, 24 (3). pp. 911-916. ISSN 0960-894X
Abstract
The enoyl acyl-carrier protein reductase (ENR) enzyme of the apicomplexan parasite family has been intensely studied for antiparasitic drug design for over a decade, with the most potent inhibitors targeting the NAD+ bound form of the enzyme. However, the higher affinity for the NADH co-factor over NAD+ and its availability in the natural environment makes the NADH complex form of ENR an attractive target. Herein, we have examined a benzimidazole family of inhibitors which target the NADH form of Francisella ENR, but despite good efficacy against Toxoplasma gondii, the IC50 for T. gondii ENR is poor, with no inhibitory activity at 1 μM. Moreover similar benzimidazole scaffolds are potent against fungi which lack the ENR enzyme and as such we believe that there may be significant off target effects for this family of inhibitors.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2013 The Authors. Published by Elsevier Ltd. Open access under CC-BY license (https://creativecommons.org/licenses/by/3.0/). |
Keywords: | Enoyl reductase; Triclosan; Toxoplasma; Benzimidazole |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 27 Jul 2017 11:07 |
Last Modified: | 27 Jul 2017 11:11 |
Published Version: | https://doi.org/10.1016/j.bmcl.2013.12.066 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.bmcl.2013.12.066 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:119440 |