Bridging in silico and in vitro perspectives to unravel molecular mechanisms underlying the inhibition of β-glucuronidase by coumarins from Hibiscus trionum

This manuscript version is made available under the CC-BY-NC-ND 4.0 licence http://creativecommons.org/licenses/by-nc-nd/4.0/

Detalles Bibliográficos
Autores: Kamel, Emadeldin M., Aba Alkhayl, Faris F., Alqhtani, Haifa A., Bin-Jumah, May, Rudayni, Hassan A., Lamsabhi, Al Mokhtar
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/720804
Acceso en línea:http://hdl.handle.net/10486/720804
https://dx.doi.org/10.1016/j.bpc.2024.107304
Access Level:acceso embargado
Palabra clave:Enzyme inhibition
Enzyme kinetics
In Vitro study
Molecular dynamic simulations
β-Glucuronidase
Química
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spelling Bridging in silico and in vitro perspectives to unravel molecular mechanisms underlying the inhibition of β-glucuronidase by coumarins from Hibiscus trionumKamel, Emadeldin M.Aba Alkhayl, Faris F.Alqhtani, Haifa A.Bin-Jumah, MayRudayni, Hassan A.Lamsabhi, Al MokhtarEnzyme inhibitionEnzyme kineticsIn Vitro studyMolecular dynamic simulationsβ-GlucuronidaseQuímicaThis manuscript version is made available under the CC-BY-NC-ND 4.0 licence http://creativecommons.org/licenses/by-nc-nd/4.0/Unraveling the intricacies of β-glucuronidase inhibition is pivotal for developing effective strategies in applications specific to gastrointestinal health and drug metabolism. Our study investigated the efficacy of some Hibiscus trionum phytochemicals as β-glucuronidase inhibitors. The results showed that cleomiscosin A and mansonone H emerged as the most potent inhibitors, with IC<inf>50</inf> values of 3.97 ± 0.35 μM and 10.32 ± 1.85 μM, respectively. Mechanistic analysis of β-glucuronidase inhibition indicated that cleomiscosin A and the reference drug EGCG displayed a mixed inhibition mode against β-glucuronidase, while mansonone H exhibited noncompetitive inhibition against β-glucuronidase. Docking studies revealed that cleomiscosin A and mansonone H exhibited the lowest binding affinities, occupying the same site as EGCG, and engaged significant key residues in their binding mechanisms. Using a 30 ns molecular dynamics (MD) simulation, we explored the interaction dynamics of isolated compounds with β-glucuronidase. Analysis of various MD parameters showed that cleomiscosin A and mansonone H exhibited consistent trajectories and significant energy stabilization with β-glucuronidase. These computational insights complemented experimental findings, underscoring the potential of cleomiscosin A and mansonone H as β-glucuronidase inhibitorsThe authors acknowledge Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2024R458), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia. Also, this work was carried out with support from the project PID2023-150717NB-I00 from Ministerio de Ciencia, Innovacion y Universidades in Spain and the project Y2020/EMT-6290 (PRIES-CM) of the Comunidad de Madrid.ElsevierDepartamento de QuímicaFacultad de Ciencias20242024-07-26research articlehttp://purl.org/coar/resource_type/c_2df8fbb1AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/720804https://dx.doi.org/10.1016/j.bpc.2024.107304reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengembargoed accesshttp://purl.org/coar/access_right/c_f1cfAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/embargoedAccessoai:repositorio.uam.es:10486/7208042026-06-23T12:46:27Z
dc.title.none.fl_str_mv Bridging in silico and in vitro perspectives to unravel molecular mechanisms underlying the inhibition of β-glucuronidase by coumarins from Hibiscus trionum
title Bridging in silico and in vitro perspectives to unravel molecular mechanisms underlying the inhibition of β-glucuronidase by coumarins from Hibiscus trionum
spellingShingle Bridging in silico and in vitro perspectives to unravel molecular mechanisms underlying the inhibition of β-glucuronidase by coumarins from Hibiscus trionum
Kamel, Emadeldin M.
Enzyme inhibition
Enzyme kinetics
In Vitro study
Molecular dynamic simulations
β-Glucuronidase
Química
title_short Bridging in silico and in vitro perspectives to unravel molecular mechanisms underlying the inhibition of β-glucuronidase by coumarins from Hibiscus trionum
title_full Bridging in silico and in vitro perspectives to unravel molecular mechanisms underlying the inhibition of β-glucuronidase by coumarins from Hibiscus trionum
title_fullStr Bridging in silico and in vitro perspectives to unravel molecular mechanisms underlying the inhibition of β-glucuronidase by coumarins from Hibiscus trionum
title_full_unstemmed Bridging in silico and in vitro perspectives to unravel molecular mechanisms underlying the inhibition of β-glucuronidase by coumarins from Hibiscus trionum
title_sort Bridging in silico and in vitro perspectives to unravel molecular mechanisms underlying the inhibition of β-glucuronidase by coumarins from Hibiscus trionum
dc.creator.none.fl_str_mv Kamel, Emadeldin M.
Aba Alkhayl, Faris F.
Alqhtani, Haifa A.
Bin-Jumah, May
Rudayni, Hassan A.
Lamsabhi, Al Mokhtar
author Kamel, Emadeldin M.
author_facet Kamel, Emadeldin M.
Aba Alkhayl, Faris F.
Alqhtani, Haifa A.
Bin-Jumah, May
Rudayni, Hassan A.
Lamsabhi, Al Mokhtar
author_role author
author2 Aba Alkhayl, Faris F.
Alqhtani, Haifa A.
Bin-Jumah, May
Rudayni, Hassan A.
Lamsabhi, Al Mokhtar
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Química
Facultad de Ciencias
dc.subject.none.fl_str_mv Enzyme inhibition
Enzyme kinetics
In Vitro study
Molecular dynamic simulations
β-Glucuronidase
Química
topic Enzyme inhibition
Enzyme kinetics
In Vitro study
Molecular dynamic simulations
β-Glucuronidase
Química
description This manuscript version is made available under the CC-BY-NC-ND 4.0 licence http://creativecommons.org/licenses/by-nc-nd/4.0/
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-07-26
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/720804
https://dx.doi.org/10.1016/j.bpc.2024.107304
url http://hdl.handle.net/10486/720804
https://dx.doi.org/10.1016/j.bpc.2024.107304
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv embargoed access
http://purl.org/coar/access_right/c_f1cf
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/embargoedAccess
rights_invalid_str_mv embargoed access
http://purl.org/coar/access_right/c_f1cf
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv embargoedAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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