Quinoline- and Isoindoline-Integrated Polycyclic Compounds as Antioxidant, and Antidiabetic Agents Targeting the Dual Inhibition of α-Glycosidase and α-Amylase Enzymes
Novel analogs of quinoline and isoindoline containing various heterocycles, such as tetrazole, triazole, pyrazole, and pyridine, were synthesized and characterized using FT-IR, NMR, and mass spectroscopy, and their antioxidant and antidiabetic activities were investigated. The previously synthesized...
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MDPI AG
2023-08-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/9/1222 |
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| author | Mohammed Al-Ghorbani Osama Alharbi Abdel-Basit Al-Odayni Naaser A. Y. Abduh |
| author_facet | Mohammed Al-Ghorbani Osama Alharbi Abdel-Basit Al-Odayni Naaser A. Y. Abduh |
| author_sort | Mohammed Al-Ghorbani |
| collection | DOAJ |
| description | Novel analogs of quinoline and isoindoline containing various heterocycles, such as tetrazole, triazole, pyrazole, and pyridine, were synthesized and characterized using FT-IR, NMR, and mass spectroscopy, and their antioxidant and antidiabetic activities were investigated. The previously synthesized compound <b>1</b> was utilized in conjugation with ketone-bearing tetrazole and isoindoline-1,3-dione to synthesize Schiff’s bases <b>2</b> and <b>3</b>. Furthermore, hydrazide <b>1</b> was treated with aryledines to provide pyrazoles <b>4a</b>–<b>c</b>. Compound <b>5</b> was obtained by treating <b>1</b> with potassium thiocyanate, which was then cyclized in a basic solution to afford triazole <b>6</b>. On the other hand, pyridine derivatives <b>7a</b>–<b>d</b> and <b>8a</b>–<b>d</b> were synthesized using 2-(4-acetylphenyl)isoindoline-1,3-dione via a one-pot condensation reaction with aryl aldehydes and active methylene compounds. From the antioxidant and antidiabetic studies, compound <b>7d</b> showed significant antioxidant activity with an EC<sub>50</sub> = 0.65, 0.52, and 0.93 mM in the free radical scavenging assays (DPPH, ABTS, and superoxide anion radicals). It also displayed noteworthy inhibitory activity against both enzymes α-glycosidase (IC<sub>50</sub>: 0.07 mM) and α-amylase (0.21 mM) compared to acarbose (0.09 mM α-glycosidase and 0.25 mM for α-amylase), and higher than in the other compounds. During in silico assays, compound <b>7d</b> exhibited favorable binding affinities towards both α-glycosidase (−10.9 kcal/mol) and α-amylase (−9.0 kcal/mol) compared to acarbose (−8.6 kcal/mol for α-glycosidase and −6.0 kcal/mol for α-amylase). The stability of <b>7d</b> was demonstrated by molecular dynamics simulations and estimations of the binding free energy throughout the simulation session (100 ns). |
| first_indexed | 2024-03-10T22:16:59Z |
| format | Article |
| id | doaj.art-2810d822976c48b4b3a1423b1bfc7dae |
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| language | English |
| last_indexed | 2024-03-10T22:16:59Z |
| publishDate | 2023-08-01 |
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| spelling | doaj.art-2810d822976c48b4b3a1423b1bfc7dae2023-11-19T12:24:16ZengMDPI AGPharmaceuticals1424-82472023-08-01169122210.3390/ph16091222Quinoline- and Isoindoline-Integrated Polycyclic Compounds as Antioxidant, and Antidiabetic Agents Targeting the Dual Inhibition of α-Glycosidase and α-Amylase EnzymesMohammed Al-Ghorbani0Osama Alharbi1Abdel-Basit Al-Odayni2Naaser A. Y. Abduh3Department of Chemistry, College of Science and Arts, Ulla, Taibah University, Madinah 41477, Saudi ArabiaDepartment of Chemistry, College of Science and Arts, Ulla, Taibah University, Madinah 41477, Saudi ArabiaDepartment of Restorative Dental Science, College of Dentistry, King Saud University, P.O. Box 60169, Riyadh 11545, Saudi ArabiaDepartment of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaNovel analogs of quinoline and isoindoline containing various heterocycles, such as tetrazole, triazole, pyrazole, and pyridine, were synthesized and characterized using FT-IR, NMR, and mass spectroscopy, and their antioxidant and antidiabetic activities were investigated. The previously synthesized compound <b>1</b> was utilized in conjugation with ketone-bearing tetrazole and isoindoline-1,3-dione to synthesize Schiff’s bases <b>2</b> and <b>3</b>. Furthermore, hydrazide <b>1</b> was treated with aryledines to provide pyrazoles <b>4a</b>–<b>c</b>. Compound <b>5</b> was obtained by treating <b>1</b> with potassium thiocyanate, which was then cyclized in a basic solution to afford triazole <b>6</b>. On the other hand, pyridine derivatives <b>7a</b>–<b>d</b> and <b>8a</b>–<b>d</b> were synthesized using 2-(4-acetylphenyl)isoindoline-1,3-dione via a one-pot condensation reaction with aryl aldehydes and active methylene compounds. From the antioxidant and antidiabetic studies, compound <b>7d</b> showed significant antioxidant activity with an EC<sub>50</sub> = 0.65, 0.52, and 0.93 mM in the free radical scavenging assays (DPPH, ABTS, and superoxide anion radicals). It also displayed noteworthy inhibitory activity against both enzymes α-glycosidase (IC<sub>50</sub>: 0.07 mM) and α-amylase (0.21 mM) compared to acarbose (0.09 mM α-glycosidase and 0.25 mM for α-amylase), and higher than in the other compounds. During in silico assays, compound <b>7d</b> exhibited favorable binding affinities towards both α-glycosidase (−10.9 kcal/mol) and α-amylase (−9.0 kcal/mol) compared to acarbose (−8.6 kcal/mol for α-glycosidase and −6.0 kcal/mol for α-amylase). The stability of <b>7d</b> was demonstrated by molecular dynamics simulations and estimations of the binding free energy throughout the simulation session (100 ns).https://www.mdpi.com/1424-8247/16/9/1222quinolineisoindolineantioxidantantidiabeticmolecular docking simulationmolecular dynamics simulation |
| spellingShingle | Mohammed Al-Ghorbani Osama Alharbi Abdel-Basit Al-Odayni Naaser A. Y. Abduh Quinoline- and Isoindoline-Integrated Polycyclic Compounds as Antioxidant, and Antidiabetic Agents Targeting the Dual Inhibition of α-Glycosidase and α-Amylase Enzymes Pharmaceuticals quinoline isoindoline antioxidant antidiabetic molecular docking simulation molecular dynamics simulation |
| title | Quinoline- and Isoindoline-Integrated Polycyclic Compounds as Antioxidant, and Antidiabetic Agents Targeting the Dual Inhibition of α-Glycosidase and α-Amylase Enzymes |
| title_full | Quinoline- and Isoindoline-Integrated Polycyclic Compounds as Antioxidant, and Antidiabetic Agents Targeting the Dual Inhibition of α-Glycosidase and α-Amylase Enzymes |
| title_fullStr | Quinoline- and Isoindoline-Integrated Polycyclic Compounds as Antioxidant, and Antidiabetic Agents Targeting the Dual Inhibition of α-Glycosidase and α-Amylase Enzymes |
| title_full_unstemmed | Quinoline- and Isoindoline-Integrated Polycyclic Compounds as Antioxidant, and Antidiabetic Agents Targeting the Dual Inhibition of α-Glycosidase and α-Amylase Enzymes |
| title_short | Quinoline- and Isoindoline-Integrated Polycyclic Compounds as Antioxidant, and Antidiabetic Agents Targeting the Dual Inhibition of α-Glycosidase and α-Amylase Enzymes |
| title_sort | quinoline and isoindoline integrated polycyclic compounds as antioxidant and antidiabetic agents targeting the dual inhibition of α glycosidase and α amylase enzymes |
| topic | quinoline isoindoline antioxidant antidiabetic molecular docking simulation molecular dynamics simulation |
| url | https://www.mdpi.com/1424-8247/16/9/1222 |
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