Structural characterization, spectroscopic profile, molecular docking, ADMET properties, molecular dynamics simulation studies, and molecular mechanics generalized born surface area analysis of 5-(Adamantan-1-yl)-4-butyl-2,4-dihydro-3H-1,2,4-triazole-3-thione as a potential COX inhibitor

Employing a synergistic combination of theoretical density functional theory (DFT) and experimental techniques, we conducted a comprehensive analysis elucidating the structural and pharmacological attributes of 5-(adamantan-1-yl)-4-butyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (5A4BT) as a potent COX...

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Autores: Al-Wahaibi, Lamya H., El-Emam, Ali A., Abdelbaky, Mohammed S. M., García-Granda, Santiago, Maurya, Anushree, Pal, Mamta, Siddiqui, Zohra, Shukla, Raj, Pathak, Shilendra K., Srivastava, Ruchi, Shukla, Vikas K., Prasad, Onkar, Sinha, Leena
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/376709
Acceso en línea:http://hdl.handle.net/10261/376709
Access Level:acceso abierto
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spelling Structural characterization, spectroscopic profile, molecular docking, ADMET properties, molecular dynamics simulation studies, and molecular mechanics generalized born surface area analysis of 5-(Adamantan-1-yl)-4-butyl-2,4-dihydro-3H-1,2,4-triazole-3-thione as a potential COX inhibitorAl-Wahaibi, Lamya H.El-Emam, Ali A.Abdelbaky, Mohammed S. M.García-Granda, SantiagoMaurya, AnushreePal, MamtaSiddiqui, ZohraShukla, RajPathak, Shilendra K.Srivastava, RuchiShukla, Vikas K.Prasad, OnkarSinha, LeenaEmploying a synergistic combination of theoretical density functional theory (DFT) and experimental techniques, we conducted a comprehensive analysis elucidating the structural and pharmacological attributes of 5-(adamantan-1-yl)-4-butyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (5A4BT) as a potent COX inhibitor. The X-ray crystallographic data of 5A4BT showed the pivotal role played by weak interactions, notably π-π and C-H-π interactions, alongside hydrogen bonding, in orchestrating the intricate supramolecular architectures within the crystalline lattice. A quantitative analysis of the arrangement of the crystal structure, as well as both inter- and intramolecular interactions, was conducted using Hirshfeld surfaces and 2D fingerprint plots. Additionally, a comprehensive examination of the IR spectra was undertaken, employing both experimental methods and theoretical DFT techniques, to elucidate the vibrational characteristics of the compound. The strength of intermolecular N-H···S hydrogen bonding and charge transfer within the system was assessed through natural bonding orbital analysis. Moreover, Bader's atoms in molecules theory was employed to estimate the strength of intermolecular hydrogen bonds, revealing strong interactions within the 5A4BT dimer. The title compound exhibited binding affinities of -6.4 and -6.5 kcal/mol for COX1 (PDB 3KK6) and COX2 (1CX2) target proteins, respectively. For the first time, predictions regarding ADMET properties, drug-likeness, and toxicity, including favorable bioavailability, along with 100 ns molecular dynamics simulations, binding free energy, and energy decomposition per residue in the binding cavity of the protein from molecular mechanics generalized born surface area approach, collectively indicate the potential of 5A4BT as a nonselective COX inhibitor.This research was funded by Princess Nourah bint Abdulrahman University Researchers Supporting Project no. (PNURSP2024R3), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia. One of the authors (R.S.) is grateful to CSIR, New Delhi, India for the research fellowship.Peer reviewedAmerican Chemical SocietyPrincess Nourah Bint Abdulrahman UniversityCouncil for Scientific and Industrial Research (India)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/376709reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1021/acsomega.4c03512Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3767092026-05-22T06:33:51Z
dc.title.none.fl_str_mv Structural characterization, spectroscopic profile, molecular docking, ADMET properties, molecular dynamics simulation studies, and molecular mechanics generalized born surface area analysis of 5-(Adamantan-1-yl)-4-butyl-2,4-dihydro-3H-1,2,4-triazole-3-thione as a potential COX inhibitor
title Structural characterization, spectroscopic profile, molecular docking, ADMET properties, molecular dynamics simulation studies, and molecular mechanics generalized born surface area analysis of 5-(Adamantan-1-yl)-4-butyl-2,4-dihydro-3H-1,2,4-triazole-3-thione as a potential COX inhibitor
spellingShingle Structural characterization, spectroscopic profile, molecular docking, ADMET properties, molecular dynamics simulation studies, and molecular mechanics generalized born surface area analysis of 5-(Adamantan-1-yl)-4-butyl-2,4-dihydro-3H-1,2,4-triazole-3-thione as a potential COX inhibitor
Al-Wahaibi, Lamya H.
title_short Structural characterization, spectroscopic profile, molecular docking, ADMET properties, molecular dynamics simulation studies, and molecular mechanics generalized born surface area analysis of 5-(Adamantan-1-yl)-4-butyl-2,4-dihydro-3H-1,2,4-triazole-3-thione as a potential COX inhibitor
title_full Structural characterization, spectroscopic profile, molecular docking, ADMET properties, molecular dynamics simulation studies, and molecular mechanics generalized born surface area analysis of 5-(Adamantan-1-yl)-4-butyl-2,4-dihydro-3H-1,2,4-triazole-3-thione as a potential COX inhibitor
title_fullStr Structural characterization, spectroscopic profile, molecular docking, ADMET properties, molecular dynamics simulation studies, and molecular mechanics generalized born surface area analysis of 5-(Adamantan-1-yl)-4-butyl-2,4-dihydro-3H-1,2,4-triazole-3-thione as a potential COX inhibitor
title_full_unstemmed Structural characterization, spectroscopic profile, molecular docking, ADMET properties, molecular dynamics simulation studies, and molecular mechanics generalized born surface area analysis of 5-(Adamantan-1-yl)-4-butyl-2,4-dihydro-3H-1,2,4-triazole-3-thione as a potential COX inhibitor
title_sort Structural characterization, spectroscopic profile, molecular docking, ADMET properties, molecular dynamics simulation studies, and molecular mechanics generalized born surface area analysis of 5-(Adamantan-1-yl)-4-butyl-2,4-dihydro-3H-1,2,4-triazole-3-thione as a potential COX inhibitor
dc.creator.none.fl_str_mv Al-Wahaibi, Lamya H.
El-Emam, Ali A.
Abdelbaky, Mohammed S. M.
García-Granda, Santiago
Maurya, Anushree
Pal, Mamta
Siddiqui, Zohra
Shukla, Raj
Pathak, Shilendra K.
Srivastava, Ruchi
Shukla, Vikas K.
Prasad, Onkar
Sinha, Leena
author Al-Wahaibi, Lamya H.
author_facet Al-Wahaibi, Lamya H.
El-Emam, Ali A.
Abdelbaky, Mohammed S. M.
García-Granda, Santiago
Maurya, Anushree
Pal, Mamta
Siddiqui, Zohra
Shukla, Raj
Pathak, Shilendra K.
Srivastava, Ruchi
Shukla, Vikas K.
Prasad, Onkar
Sinha, Leena
author_role author
author2 El-Emam, Ali A.
Abdelbaky, Mohammed S. M.
García-Granda, Santiago
Maurya, Anushree
Pal, Mamta
Siddiqui, Zohra
Shukla, Raj
Pathak, Shilendra K.
Srivastava, Ruchi
Shukla, Vikas K.
Prasad, Onkar
Sinha, Leena
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Princess Nourah Bint Abdulrahman University
Council for Scientific and Industrial Research (India)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description Employing a synergistic combination of theoretical density functional theory (DFT) and experimental techniques, we conducted a comprehensive analysis elucidating the structural and pharmacological attributes of 5-(adamantan-1-yl)-4-butyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (5A4BT) as a potent COX inhibitor. The X-ray crystallographic data of 5A4BT showed the pivotal role played by weak interactions, notably π-π and C-H-π interactions, alongside hydrogen bonding, in orchestrating the intricate supramolecular architectures within the crystalline lattice. A quantitative analysis of the arrangement of the crystal structure, as well as both inter- and intramolecular interactions, was conducted using Hirshfeld surfaces and 2D fingerprint plots. Additionally, a comprehensive examination of the IR spectra was undertaken, employing both experimental methods and theoretical DFT techniques, to elucidate the vibrational characteristics of the compound. The strength of intermolecular N-H···S hydrogen bonding and charge transfer within the system was assessed through natural bonding orbital analysis. Moreover, Bader's atoms in molecules theory was employed to estimate the strength of intermolecular hydrogen bonds, revealing strong interactions within the 5A4BT dimer. The title compound exhibited binding affinities of -6.4 and -6.5 kcal/mol for COX1 (PDB 3KK6) and COX2 (1CX2) target proteins, respectively. For the first time, predictions regarding ADMET properties, drug-likeness, and toxicity, including favorable bioavailability, along with 100 ns molecular dynamics simulations, binding free energy, and energy decomposition per residue in the binding cavity of the protein from molecular mechanics generalized born surface area approach, collectively indicate the potential of 5A4BT as a nonselective COX inhibitor.
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/376709
url http://hdl.handle.net/10261/376709
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1021/acsomega.4c03512
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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repository.mail.fl_str_mv
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