Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics

Autores
Shahzad, Danish; Saeed, Aamer; Larik, Fayaz Ali; Channar, Pervaiz Ali; Abbas, Qamar; Alajmi, Mohamed F.; Arshad, M. Ifzan; Erben, Mauricio Federico; Hassan, Mubashir; Raza, Hussain; Seo, Sung-Yum; El-Seedi, Hesham R.
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A series of symmetrical salicylaldehyde-bishydrazine azo molecules, 5a–5h, have been synthesized, characterized by 1H-NMR and 13C-NMR, and evaluated for their in vitro α-glucosidase and α-amylase inhibitory activities. All the synthesized compounds efficiently inhibited both enzymes. Compound 5g was the most potent derivative in the series, and powerfully inhibited both α-glucosidase and α-amylase. The IC50 of 5g against α-glucosidase was 0.35917 ± 0.0189 µM (standard acarbose IC50 = 6.109 ± 0.329 µM), and the IC50 value of 5g against α-amylase was 0.4379 ± 0.0423 µM (standard acarbose IC50 = 33.178 ± 2.392 µM). The Lineweaver-Burk plot indicated that compound 5g is a competitive inhibitor of α-glucosidase. The binding interactions of the most active analogues were confirmed through molecular docking studies. Docking studies showed that 5g interacts with the residues Trp690, Asp548, Arg425, and Glu426, which form hydrogen bonds to 5g with distances of 2.05, 2.20, 2.10 and 2.18 Å, respectively. All compounds showed high mutagenic and tumorigenic behaviors, and only 5e showed irritant properties. In addition, all the derivatives showed good antioxidant activities. The pharmacokinetic evaluation also revealed promising results.
Facultad de Ciencias Exactas
Centro de Química Inorgánica
Materia
Ciencias Exactas
Química
bis-azo Schiff bases
dual inhibitor
α-glucosidase inhibitor
α-amylase
antioxidant
SAR
chemo-informatics
kinetic mechanism
molecular docking
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/107656
Acceder
id SEDICI_40e5bbb51d5aedf1bd673ed87c101f2f
oai_identifier_str oai:sedici.unlp.edu.ar:10915/107656
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and PharmacokineticsShahzad, DanishSaeed, AamerLarik, Fayaz AliChannar, Pervaiz AliAbbas, QamarAlajmi, Mohamed F.Arshad, M. IfzanErben, Mauricio FedericoHassan, MubashirRaza, HussainSeo, Sung-YumEl-Seedi, Hesham R.Ciencias ExactasQuímicabis-azo Schiff basesdual inhibitorα-glucosidase inhibitorα-amylaseantioxidantSARchemo-informaticskinetic mechanismmolecular dockingA series of symmetrical salicylaldehyde-bishydrazine azo molecules, 5a–5h, have been synthesized, characterized by <sup>1</sup>H-NMR and <sup>13</sup>C-NMR, and evaluated for their in vitro α-glucosidase and α-amylase inhibitory activities. All the synthesized compounds efficiently inhibited both enzymes. Compound 5g was the most potent derivative in the series, and powerfully inhibited both α-glucosidase and α-amylase. The IC<sub>50</sub> of 5g against α-glucosidase was 0.35917 ± 0.0189 µM (standard acarbose IC<sub>50</sub> = 6.109 ± 0.329 µM), and the IC<sub>50</sub> value of 5g against α-amylase was 0.4379 ± 0.0423 µM (standard acarbose IC<sub>50</sub> = 33.178 ± 2.392 µM). The Lineweaver-Burk plot indicated that compound 5g is a competitive inhibitor of α-glucosidase. The binding interactions of the most active analogues were confirmed through molecular docking studies. Docking studies showed that 5g interacts with the residues Trp690, Asp548, Arg425, and Glu426, which form hydrogen bonds to 5g with distances of 2.05, 2.20, 2.10 and 2.18 Å, respectively. All compounds showed high mutagenic and tumorigenic behaviors, and only 5e showed irritant properties. In addition, all the derivatives showed good antioxidant activities. The pharmacokinetic evaluation also revealed promising results.Facultad de Ciencias ExactasCentro de Química Inorgánica2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/107656enginfo:eu-repo/semantics/altIdentifier/url/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6515238&blobtype=pdfinfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1420-3049/24/8/1511info:eu-repo/semantics/altIdentifier/issn/1420-3049info:eu-repo/semantics/altIdentifier/pmid/30999646info:eu-repo/semantics/altIdentifier/doi/10.3390/molecules24081511info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-17T10:06:39Zoai:sedici.unlp.edu.ar:10915/107656Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-17 10:06:39.517SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics
title Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics
spellingShingle Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics
Shahzad, Danish
Ciencias Exactas
Química
bis-azo Schiff bases
dual inhibitor
α-glucosidase inhibitor
α-amylase
antioxidant
SAR
chemo-informatics
kinetic mechanism
molecular docking
title_short Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics
title_full Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics
title_fullStr Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics
title_full_unstemmed Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics
title_sort Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics
dc.creator.none.fl_str_mv Shahzad, Danish
Saeed, Aamer
Larik, Fayaz Ali
Channar, Pervaiz Ali
Abbas, Qamar
Alajmi, Mohamed F.
Arshad, M. Ifzan
Erben, Mauricio Federico
Hassan, Mubashir
Raza, Hussain
Seo, Sung-Yum
El-Seedi, Hesham R.
author Shahzad, Danish
author_facet Shahzad, Danish
Saeed, Aamer
Larik, Fayaz Ali
Channar, Pervaiz Ali
Abbas, Qamar
Alajmi, Mohamed F.
Arshad, M. Ifzan
Erben, Mauricio Federico
Hassan, Mubashir
Raza, Hussain
Seo, Sung-Yum
El-Seedi, Hesham R.
author_role author
author2 Saeed, Aamer
Larik, Fayaz Ali
Channar, Pervaiz Ali
Abbas, Qamar
Alajmi, Mohamed F.
Arshad, M. Ifzan
Erben, Mauricio Federico
Hassan, Mubashir
Raza, Hussain
Seo, Sung-Yum
El-Seedi, Hesham R.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Exactas
Química
bis-azo Schiff bases
dual inhibitor
α-glucosidase inhibitor
α-amylase
antioxidant
SAR
chemo-informatics
kinetic mechanism
molecular docking
topic Ciencias Exactas
Química
bis-azo Schiff bases
dual inhibitor
α-glucosidase inhibitor
α-amylase
antioxidant
SAR
chemo-informatics
kinetic mechanism
molecular docking
dc.description.none.fl_txt_mv A series of symmetrical salicylaldehyde-bishydrazine azo molecules, 5a–5h, have been synthesized, characterized by <sup>1</sup>H-NMR and <sup>13</sup>C-NMR, and evaluated for their in vitro α-glucosidase and α-amylase inhibitory activities. All the synthesized compounds efficiently inhibited both enzymes. Compound 5g was the most potent derivative in the series, and powerfully inhibited both α-glucosidase and α-amylase. The IC<sub>50</sub> of 5g against α-glucosidase was 0.35917 ± 0.0189 µM (standard acarbose IC<sub>50</sub> = 6.109 ± 0.329 µM), and the IC<sub>50</sub> value of 5g against α-amylase was 0.4379 ± 0.0423 µM (standard acarbose IC<sub>50</sub> = 33.178 ± 2.392 µM). The Lineweaver-Burk plot indicated that compound 5g is a competitive inhibitor of α-glucosidase. The binding interactions of the most active analogues were confirmed through molecular docking studies. Docking studies showed that 5g interacts with the residues Trp690, Asp548, Arg425, and Glu426, which form hydrogen bonds to 5g with distances of 2.05, 2.20, 2.10 and 2.18 Å, respectively. All compounds showed high mutagenic and tumorigenic behaviors, and only 5e showed irritant properties. In addition, all the derivatives showed good antioxidant activities. The pharmacokinetic evaluation also revealed promising results.
Facultad de Ciencias Exactas
Centro de Química Inorgánica
description A series of symmetrical salicylaldehyde-bishydrazine azo molecules, 5a–5h, have been synthesized, characterized by <sup>1</sup>H-NMR and <sup>13</sup>C-NMR, and evaluated for their in vitro α-glucosidase and α-amylase inhibitory activities. All the synthesized compounds efficiently inhibited both enzymes. Compound 5g was the most potent derivative in the series, and powerfully inhibited both α-glucosidase and α-amylase. The IC<sub>50</sub> of 5g against α-glucosidase was 0.35917 ± 0.0189 µM (standard acarbose IC<sub>50</sub> = 6.109 ± 0.329 µM), and the IC<sub>50</sub> value of 5g against α-amylase was 0.4379 ± 0.0423 µM (standard acarbose IC<sub>50</sub> = 33.178 ± 2.392 µM). The Lineweaver-Burk plot indicated that compound 5g is a competitive inhibitor of α-glucosidase. The binding interactions of the most active analogues were confirmed through molecular docking studies. Docking studies showed that 5g interacts with the residues Trp690, Asp548, Arg425, and Glu426, which form hydrogen bonds to 5g with distances of 2.05, 2.20, 2.10 and 2.18 Å, respectively. All compounds showed high mutagenic and tumorigenic behaviors, and only 5e showed irritant properties. In addition, all the derivatives showed good antioxidant activities. The pharmacokinetic evaluation also revealed promising results.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/107656
url http://sedici.unlp.edu.ar/handle/10915/107656
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6515238&blobtype=pdf
info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1420-3049/24/8/1511
info:eu-repo/semantics/altIdentifier/issn/1420-3049
info:eu-repo/semantics/altIdentifier/pmid/30999646
info:eu-repo/semantics/altIdentifier/doi/10.3390/molecules24081511
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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score 13.000565

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