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Thiazolidin-2-cyanamides derivatives as novel potent Escherichia coli β-glucuronidase inhibitors and their structure–inhibitory activity relationships
Gut microbial β-glucuronidases have the ability to deconjugate glucuronides of some drugs, thus have been considered as an important drug target to alleviate the drug metabolites-induced gastrointestinal toxicity. In this study, thiazolidin-2-cyanamide derivatives containing 5-phenyl-2-furan moiety...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534389/ https://www.ncbi.nlm.nih.gov/pubmed/32928007 http://dx.doi.org/10.1080/14756366.2020.1816998 |
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author | Zhou, Tao-Shun Wei, Bin He, Min Li, Ya-Sheng Wang, Ya-Kun Wang, Si-Jia Chen, Jian-Wei Zhang, Hua-Wei Cui, Zi-Ning Wang, Hong |
author_facet | Zhou, Tao-Shun Wei, Bin He, Min Li, Ya-Sheng Wang, Ya-Kun Wang, Si-Jia Chen, Jian-Wei Zhang, Hua-Wei Cui, Zi-Ning Wang, Hong |
author_sort | Zhou, Tao-Shun |
collection | PubMed |
description | Gut microbial β-glucuronidases have the ability to deconjugate glucuronides of some drugs, thus have been considered as an important drug target to alleviate the drug metabolites-induced gastrointestinal toxicity. In this study, thiazolidin-2-cyanamide derivatives containing 5-phenyl-2-furan moiety (1–13) were evaluated for inhibitory activity against Escherichia coli β-glucuronidase (EcGUS). All of them showed more potent inhibition than a commonly used positive control, d-saccharic acid 1,4-lactone, with the IC(50) values ranging from 1.2 µM to 23.1 µM. Inhibition kinetics studies indicated that compound 1–3 were competitive type inhibitors for EcGUS. Molecular docking studies were performed and predicted the potential molecular determinants for their potent inhibitory effects towards EcGUS. Structure–inhibitory activity relationship study revealed that chloro substitution on the phenyl moiety was essential for EcGUS inhibition, which would help researchers to design and develop more effective thiazolidin-2-cyanamide type inhibitors against EcGUS. |
format | Online Article Text |
id | pubmed-7534389 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-75343892020-10-14 Thiazolidin-2-cyanamides derivatives as novel potent Escherichia coli β-glucuronidase inhibitors and their structure–inhibitory activity relationships Zhou, Tao-Shun Wei, Bin He, Min Li, Ya-Sheng Wang, Ya-Kun Wang, Si-Jia Chen, Jian-Wei Zhang, Hua-Wei Cui, Zi-Ning Wang, Hong J Enzyme Inhib Med Chem Research Paper Gut microbial β-glucuronidases have the ability to deconjugate glucuronides of some drugs, thus have been considered as an important drug target to alleviate the drug metabolites-induced gastrointestinal toxicity. In this study, thiazolidin-2-cyanamide derivatives containing 5-phenyl-2-furan moiety (1–13) were evaluated for inhibitory activity against Escherichia coli β-glucuronidase (EcGUS). All of them showed more potent inhibition than a commonly used positive control, d-saccharic acid 1,4-lactone, with the IC(50) values ranging from 1.2 µM to 23.1 µM. Inhibition kinetics studies indicated that compound 1–3 were competitive type inhibitors for EcGUS. Molecular docking studies were performed and predicted the potential molecular determinants for their potent inhibitory effects towards EcGUS. Structure–inhibitory activity relationship study revealed that chloro substitution on the phenyl moiety was essential for EcGUS inhibition, which would help researchers to design and develop more effective thiazolidin-2-cyanamide type inhibitors against EcGUS. Taylor & Francis 2020-09-14 /pmc/articles/PMC7534389/ /pubmed/32928007 http://dx.doi.org/10.1080/14756366.2020.1816998 Text en © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Zhou, Tao-Shun Wei, Bin He, Min Li, Ya-Sheng Wang, Ya-Kun Wang, Si-Jia Chen, Jian-Wei Zhang, Hua-Wei Cui, Zi-Ning Wang, Hong Thiazolidin-2-cyanamides derivatives as novel potent Escherichia coli β-glucuronidase inhibitors and their structure–inhibitory activity relationships |
title | Thiazolidin-2-cyanamides derivatives as novel potent Escherichia coli β-glucuronidase inhibitors and their structure–inhibitory activity relationships |
title_full | Thiazolidin-2-cyanamides derivatives as novel potent Escherichia coli β-glucuronidase inhibitors and their structure–inhibitory activity relationships |
title_fullStr | Thiazolidin-2-cyanamides derivatives as novel potent Escherichia coli β-glucuronidase inhibitors and their structure–inhibitory activity relationships |
title_full_unstemmed | Thiazolidin-2-cyanamides derivatives as novel potent Escherichia coli β-glucuronidase inhibitors and their structure–inhibitory activity relationships |
title_short | Thiazolidin-2-cyanamides derivatives as novel potent Escherichia coli β-glucuronidase inhibitors and their structure–inhibitory activity relationships |
title_sort | thiazolidin-2-cyanamides derivatives as novel potent escherichia coli β-glucuronidase inhibitors and their structure–inhibitory activity relationships |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534389/ https://www.ncbi.nlm.nih.gov/pubmed/32928007 http://dx.doi.org/10.1080/14756366.2020.1816998 |
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