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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| Main Authors: | , , , |
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| Format: | Book |
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MDPI AG,
2023-08-01T00:00:00Z.
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| Summary: | 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). |
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| Item Description: | 10.3390/ph16091222 1424-8247 |