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 compound was utilized in conjugation with ketone-bearing tetrazole and isoindoline-1,3-dione to synthesize Schiff's bases and . Furthermore, hydrazide was treated with aryledines to provide pyrazoles -. Compound was obtained by treating with potassium thiocyanate, which was then cyclized in a basic solution to afford triazole . On the other hand, pyridine derivatives - and - 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 showed significant antioxidant activity with an EC = 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: 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 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 was demonstrated by molecular dynamics simulations and estimations of the binding free energy throughout the simulation session (100 ns).