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Expression, Purification, and Comparative Inhibition of Helicobacter pylori Urease by Regio-Selectively Alkylated Benzimidazole 2-Thione Derivatives
The urease enzyme has been an important target for the discovery of effective pharmacological and agricultural products. Thirteen regio-selectively alkylated benzimidazole-2-thione derivatives have been designed to carry the essential features of urease inhibitors. The urease enzyme was isolated fro...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8838460/ https://www.ncbi.nlm.nih.gov/pubmed/35164122 http://dx.doi.org/10.3390/molecules27030865 |
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author | Mohammed, Salih Osman El Ashry, El Sayed H. Khalid, Asaad Amer, Mohamed R. Metwaly, Ahmed M. Eissa, Ibrahim H. Elkaeed, Eslam B. Elshobaky, Ahmed Hafez, Elsayed E. |
author_facet | Mohammed, Salih Osman El Ashry, El Sayed H. Khalid, Asaad Amer, Mohamed R. Metwaly, Ahmed M. Eissa, Ibrahim H. Elkaeed, Eslam B. Elshobaky, Ahmed Hafez, Elsayed E. |
author_sort | Mohammed, Salih Osman |
collection | PubMed |
description | The urease enzyme has been an important target for the discovery of effective pharmacological and agricultural products. Thirteen regio-selectively alkylated benzimidazole-2-thione derivatives have been designed to carry the essential features of urease inhibitors. The urease enzyme was isolated from Helicobacter pylori as a recombinant urease utilizing the His-tag method. The isolated enzyme was purified and characterized using chromatographic and FPLC techniques showing a maximal activity of 200 mg/mL. Additionally, the commercial Jack bean urease was purchased and included in this study for comparative and mechanistic investigations. The designed compounds were synthesized and screened for their inhibitory activity against the two ureases. Compound 2 inhibited H. pylori and Jack bean ureases with IC(50) values of 0.11; and 0.26 mM; respectively. While compound 5 showed IC(50) values of 0.01; and 0.29 mM; respectively. Compounds 2 and 5 were docked against Helicobacter pylori urease (PDB ID: 1E9Y; resolution: 3.00 Å) and exhibited correct binding modes with free energy (ΔG) values of −9.74 and −13.82 kcal mol(−1); respectively. Further; the in silico ADMET and toxicity properties of 2 and 5 indicated their general safeties and likeness to be used as drugs. Finally, the compounds’ safety was authenticated by an in vitro cytotoxicity assay against fibroblast cells. |
format | Online Article Text |
id | pubmed-8838460 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88384602022-02-13 Expression, Purification, and Comparative Inhibition of Helicobacter pylori Urease by Regio-Selectively Alkylated Benzimidazole 2-Thione Derivatives Mohammed, Salih Osman El Ashry, El Sayed H. Khalid, Asaad Amer, Mohamed R. Metwaly, Ahmed M. Eissa, Ibrahim H. Elkaeed, Eslam B. Elshobaky, Ahmed Hafez, Elsayed E. Molecules Article The urease enzyme has been an important target for the discovery of effective pharmacological and agricultural products. Thirteen regio-selectively alkylated benzimidazole-2-thione derivatives have been designed to carry the essential features of urease inhibitors. The urease enzyme was isolated from Helicobacter pylori as a recombinant urease utilizing the His-tag method. The isolated enzyme was purified and characterized using chromatographic and FPLC techniques showing a maximal activity of 200 mg/mL. Additionally, the commercial Jack bean urease was purchased and included in this study for comparative and mechanistic investigations. The designed compounds were synthesized and screened for their inhibitory activity against the two ureases. Compound 2 inhibited H. pylori and Jack bean ureases with IC(50) values of 0.11; and 0.26 mM; respectively. While compound 5 showed IC(50) values of 0.01; and 0.29 mM; respectively. Compounds 2 and 5 were docked against Helicobacter pylori urease (PDB ID: 1E9Y; resolution: 3.00 Å) and exhibited correct binding modes with free energy (ΔG) values of −9.74 and −13.82 kcal mol(−1); respectively. Further; the in silico ADMET and toxicity properties of 2 and 5 indicated their general safeties and likeness to be used as drugs. Finally, the compounds’ safety was authenticated by an in vitro cytotoxicity assay against fibroblast cells. MDPI 2022-01-27 /pmc/articles/PMC8838460/ /pubmed/35164122 http://dx.doi.org/10.3390/molecules27030865 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mohammed, Salih Osman El Ashry, El Sayed H. Khalid, Asaad Amer, Mohamed R. Metwaly, Ahmed M. Eissa, Ibrahim H. Elkaeed, Eslam B. Elshobaky, Ahmed Hafez, Elsayed E. Expression, Purification, and Comparative Inhibition of Helicobacter pylori Urease by Regio-Selectively Alkylated Benzimidazole 2-Thione Derivatives |
title | Expression, Purification, and Comparative Inhibition of Helicobacter pylori Urease by Regio-Selectively Alkylated Benzimidazole 2-Thione Derivatives |
title_full | Expression, Purification, and Comparative Inhibition of Helicobacter pylori Urease by Regio-Selectively Alkylated Benzimidazole 2-Thione Derivatives |
title_fullStr | Expression, Purification, and Comparative Inhibition of Helicobacter pylori Urease by Regio-Selectively Alkylated Benzimidazole 2-Thione Derivatives |
title_full_unstemmed | Expression, Purification, and Comparative Inhibition of Helicobacter pylori Urease by Regio-Selectively Alkylated Benzimidazole 2-Thione Derivatives |
title_short | Expression, Purification, and Comparative Inhibition of Helicobacter pylori Urease by Regio-Selectively Alkylated Benzimidazole 2-Thione Derivatives |
title_sort | expression, purification, and comparative inhibition of helicobacter pylori urease by regio-selectively alkylated benzimidazole 2-thione derivatives |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8838460/ https://www.ncbi.nlm.nih.gov/pubmed/35164122 http://dx.doi.org/10.3390/molecules27030865 |
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