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Novel 2-arylthiopropanoyl-CoA inhibitors of α-methylacyl-CoA racemase 1A (AMACR; P504S) as potential anti-prostate cancer agents

Yevglevskis, Maksims, Nathubhai, Amit, Wadda, Katty, Lee, Guat, Al-Rawi, Suzanne, Jiao, Tingying, Mitchell, Paul, J., James, Tony, D., Threadgill, Michael, D., Woodman, Timothy, J. and Lloyd, Matthew, D. (2019) Novel 2-arylthiopropanoyl-CoA inhibitors of α-methylacyl-CoA racemase 1A (AMACR; P504S) as potential anti-prostate cancer agents. Bioorganic Chemistry, 92 (103263). pp. 1-8. ISSN 0045-2068

Item Type: Article


α-Methylacyl-CoA racemase (AMACR; P504S) catalyses an essential step in the degradation of branched-chain
fatty acids and the activation of ibuprofen and related drugs. AMACR has gained much attention as a drug target
and biomarker, since it is found at elevated levels in prostate cancer and several other cancers. Herein, we report the synthesis of 2-(phenylthio)propanoyl-CoA derivatives which provided potent AMACR inhibitory activity(IC50=22–100 nM), as measured by the AMACR colorimetric activity assay. Inhibitor potency positively correlates with calculated logP, although 2-(3-benzyloxyphenylthio)propanoyl-CoA and 2-(4-(2-methylpropoxy)phenylthio)propanoyl-CoA were more potent than predicted by this parameter. Subsequently, carboxylic acid precursors were evaluated against androgen-dependent LnCaP prostate cancer cells and androgen-independent Du145 and PC3 prostate cancer cells using the MTS assay. All tested precursor acids showed inhibitory activity against LnCaP, Du145 and PC3 cells at 500 μM, but lacked activity at 100 μM. This is the first extensive structureactivity relationship study on the influence of side-chain interactions on the potency of novel rationally designed AMACR inhibitors.

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Depositing User: Amit Nathubhai


Item ID: 11122
Identification Number:
ISSN: 0045-2068
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ORCID for Amit Nathubhai: ORCID iD

Catalogue record

Date Deposited: 19 Sep 2019 10:12
Last Modified: 30 Sep 2020 10:46


Author: Amit Nathubhai ORCID iD
Author: Maksims Yevglevskis
Author: Katty Wadda
Author: Guat Lee
Author: Suzanne Al-Rawi
Author: Tingying Jiao
Author: Paul, J. Mitchell
Author: Tony, D. James
Author: Michael, D. Threadgill
Author: Timothy, J. Woodman
Author: Matthew, D. Lloyd

University Divisions

Faculty of Health Sciences and Wellbeing
Faculty of Health Sciences and Wellbeing > School of Pharmacy and Pharmaceutical Sciences


Sciences > Chemistry

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