Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics
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 effic...
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| Autores principales: | , , , , , , , , , , , |
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| Formato: | Articulo |
| Lenguaje: | Inglés |
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2019
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| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/107656 http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6515238&blobtype=pdf https://www.mdpi.com/1420-3049/24/8/1511 |
| Aporte de: |
| id |
I19-R120-10915-107656 |
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| record_format |
dspace |
| institution |
Universidad Nacional de La Plata |
| institution_str |
I-19 |
| repository_str |
R-120 |
| collection |
SEDICI (UNLP) |
| language |
Inglés |
| topic |
Ciencias Exactas Química bis-azo Schiff bases dual inhibitor α-glucosidase inhibitor α-amylase antioxidant SAR chemo-informatics kinetic mechanism molecular docking |
| spellingShingle |
Ciencias Exactas Química bis-azo Schiff bases dual inhibitor α-glucosidase inhibitor α-amylase antioxidant SAR chemo-informatics kinetic mechanism molecular docking 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. Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics |
| topic_facet |
Ciencias Exactas Química bis-azo Schiff bases dual inhibitor α-glucosidase inhibitor α-amylase antioxidant SAR chemo-informatics kinetic mechanism molecular docking |
| 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. |
| format |
Articulo Articulo |
| author |
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_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_sort |
Shahzad, Danish |
| title |
Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics |
| 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 |
| publishDate |
2019 |
| url |
http://sedici.unlp.edu.ar/handle/10915/107656 http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6515238&blobtype=pdf https://www.mdpi.com/1420-3049/24/8/1511 |
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