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.; Ifzan Arshad, M.; 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 1 H-NMR and 13 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 50 of 5g against α-glucosidase was 0.35917 ± 0.0189 µM (standard acarbose IC 50 = 6.109 ± 0.329 µM), and the IC 50 value of 5g against α-amylase was 0.4379 ± 0.0423 µM (standard acarbose IC 50 = 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.
Fil: Shahzad, Danish. Quaid-i-azam University; Pakistán
Fil: Saeed, Aamer. Quaid-i-azam University; Pakistán
Fil: Larik, Fayaz Ali. Quaid-i-azam University; Pakistán
Fil: Channar, Pervaiz Ali. Quaid-i-azam University; Pakistán
Fil: Abbas, Qamar. University Of Sindh; Pakistán
Fil: Alajmi, Mohamed F.. King Saud University College Of Pharmacy; Arabia Saudita
Fil: Ifzan Arshad, M.. Quaid-i-azam University; Pakistán
Fil: Erben, Mauricio Federico. Facultad de Ciencias Exactas, Universidad Nacional de la Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Hassan, Mubashir. Kongju National University; Corea del Sur
Fil: Raza, Hussain. Kongju National University; Corea del Sur
Fil: Seo, Sung-Yum. Kongju National University; Corea del Sur
Fil: El-Seedi, Hesham R.. Uppsala Biomedicinska Centrum; Suecia - Materia
-
ANTIOXIDANT
BIS-AZO SCHIFF BASES
CHEMO-INFORMATICS
DUAL INHIBITOR
KINETIC MECHANISM
MOLECULAR DOCKING
SAR
Α-AMYLASE
Α-GLUCOSIDASE INHIBITOR - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/124806
Ver los metadatos del registro completo
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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.Ifzan Arshad, M.Erben, Mauricio FedericoHassan, MubashirRaza, HussainSeo, Sung-YumEl-Seedi, Hesham R.ANTIOXIDANTBIS-AZO SCHIFF BASESCHEMO-INFORMATICSDUAL INHIBITORKINETIC MECHANISMMOLECULAR DOCKINGSARΑ-AMYLASEΑ-GLUCOSIDASE INHIBITORhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1A series of symmetrical salicylaldehyde-bishydrazine azo molecules, 5a?5h, have been synthesized, characterized by 1 H-NMR and 13 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 50 of 5g against α-glucosidase was 0.35917 ± 0.0189 µM (standard acarbose IC 50 = 6.109 ± 0.329 µM), and the IC 50 value of 5g against α-amylase was 0.4379 ± 0.0423 µM (standard acarbose IC 50 = 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.Fil: Shahzad, Danish. Quaid-i-azam University; PakistánFil: Saeed, Aamer. Quaid-i-azam University; PakistánFil: Larik, Fayaz Ali. Quaid-i-azam University; PakistánFil: Channar, Pervaiz Ali. Quaid-i-azam University; PakistánFil: Abbas, Qamar. University Of Sindh; PakistánFil: Alajmi, Mohamed F.. King Saud University College Of Pharmacy; Arabia SauditaFil: Ifzan Arshad, M.. Quaid-i-azam University; PakistánFil: Erben, Mauricio Federico. Facultad de Ciencias Exactas, Universidad Nacional de la Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Hassan, Mubashir. Kongju National University; Corea del SurFil: Raza, Hussain. Kongju National University; Corea del SurFil: Seo, Sung-Yum. Kongju National University; Corea del SurFil: El-Seedi, Hesham R.. Uppsala Biomedicinska Centrum; SueciaMolecular Diversity Preservation International2019-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/124806Shahzad, Danish; Saeed, Aamer; Larik, Fayaz Ali; Channar, Pervaiz Ali; Abbas, Qamar; et al.; Novel C-2 symmetric molecules as α-glucosidase and α-amylase inhibitors: Design, synthesis, kinetic evaluation, molecular docking and pharmacokinetics; Molecular Diversity Preservation International; Molecules; 24; 8; 4-2019; 1-161420-3049CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/molecules24081511info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1420-3049/24/8/1511info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:10:04Zoai:ri.conicet.gov.ar:11336/124806instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:10:04.356CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| 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 ANTIOXIDANT BIS-AZO SCHIFF BASES CHEMO-INFORMATICS DUAL INHIBITOR KINETIC MECHANISM MOLECULAR DOCKING SAR Α-AMYLASE Α-GLUCOSIDASE INHIBITOR |
| 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. Ifzan Arshad, M. 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. Ifzan Arshad, M. 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. Ifzan Arshad, M. 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 |
ANTIOXIDANT BIS-AZO SCHIFF BASES CHEMO-INFORMATICS DUAL INHIBITOR KINETIC MECHANISM MOLECULAR DOCKING SAR Α-AMYLASE Α-GLUCOSIDASE INHIBITOR |
| topic |
ANTIOXIDANT BIS-AZO SCHIFF BASES CHEMO-INFORMATICS DUAL INHIBITOR KINETIC MECHANISM MOLECULAR DOCKING SAR Α-AMYLASE Α-GLUCOSIDASE INHIBITOR |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.4 https://purl.org/becyt/ford/1 |
| dc.description.none.fl_txt_mv |
A series of symmetrical salicylaldehyde-bishydrazine azo molecules, 5a?5h, have been synthesized, characterized by 1 H-NMR and 13 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 50 of 5g against α-glucosidase was 0.35917 ± 0.0189 µM (standard acarbose IC 50 = 6.109 ± 0.329 µM), and the IC 50 value of 5g against α-amylase was 0.4379 ± 0.0423 µM (standard acarbose IC 50 = 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. Fil: Shahzad, Danish. Quaid-i-azam University; Pakistán Fil: Saeed, Aamer. Quaid-i-azam University; Pakistán Fil: Larik, Fayaz Ali. Quaid-i-azam University; Pakistán Fil: Channar, Pervaiz Ali. Quaid-i-azam University; Pakistán Fil: Abbas, Qamar. University Of Sindh; Pakistán Fil: Alajmi, Mohamed F.. King Saud University College Of Pharmacy; Arabia Saudita Fil: Ifzan Arshad, M.. Quaid-i-azam University; Pakistán Fil: Erben, Mauricio Federico. Facultad de Ciencias Exactas, Universidad Nacional de la Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Hassan, Mubashir. Kongju National University; Corea del Sur Fil: Raza, Hussain. Kongju National University; Corea del Sur Fil: Seo, Sung-Yum. Kongju National University; Corea del Sur Fil: El-Seedi, Hesham R.. Uppsala Biomedicinska Centrum; Suecia |
| description |
A series of symmetrical salicylaldehyde-bishydrazine azo molecules, 5a?5h, have been synthesized, characterized by 1 H-NMR and 13 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 50 of 5g against α-glucosidase was 0.35917 ± 0.0189 µM (standard acarbose IC 50 = 6.109 ± 0.329 µM), and the IC 50 value of 5g against α-amylase was 0.4379 ± 0.0423 µM (standard acarbose IC 50 = 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 |
2019-04 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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://hdl.handle.net/11336/124806 Shahzad, Danish; Saeed, Aamer; Larik, Fayaz Ali; Channar, Pervaiz Ali; Abbas, Qamar; et al.; Novel C-2 symmetric molecules as α-glucosidase and α-amylase inhibitors: Design, synthesis, kinetic evaluation, molecular docking and pharmacokinetics; Molecular Diversity Preservation International; Molecules; 24; 8; 4-2019; 1-16 1420-3049 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/124806 |
| identifier_str_mv |
Shahzad, Danish; Saeed, Aamer; Larik, Fayaz Ali; Channar, Pervaiz Ali; Abbas, Qamar; et al.; Novel C-2 symmetric molecules as α-glucosidase and α-amylase inhibitors: Design, synthesis, kinetic evaluation, molecular docking and pharmacokinetics; Molecular Diversity Preservation International; Molecules; 24; 8; 4-2019; 1-16 1420-3049 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
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info:eu-repo/semantics/altIdentifier/doi/10.3390/molecules24081511 info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1420-3049/24/8/1511 |
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info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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openAccess |
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https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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application/pdf application/pdf |
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Molecular Diversity Preservation International |
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Molecular Diversity Preservation International |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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