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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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