Exploration of 1,3,4‐oxadiazoles Engrafted With Indole and Phthalimide Scaffolds as Multi Target Peroxidase, Acetylcholinesterase, and Butyrylchloinesterase Inhibitors: Synthesis, DFT Calculations, and Molecular Docking Studies

Abstract Here, we present the structural and pharmacological characteristics of 2‐(4‐(5‐(3,5‐disubstituted‐1 H ‐indol‐2‐yl)‐1,3,4‐oxadiazol‐2‐yl)phenyl)isoindoline‐1,3‐diones 5(a‐h) as a strong antioxidant and anti‐Alzheimer's disease activity using a synergistic combination of theoretical and experimental techniques. The structures of novel compounds were analyzed by spectral analysis (IR, NMR and Mass spectrometry). DFT calculations were analyzed for the selected compounds by applying the B3LYP hybrid functional and the 6–31G (d, p) basis set. The predictions regarding ADMET properties, drug‐likeness, and toxicity, including favorable bioavailability of all the synthesized compounds were disclosed. All the newly synthesized compounds 5(a–h) were illustrated well to comparable inhibitory potentials ranging from IC 50 values 12.12 ± 0.02 µM to 36.31 ± 0.26 µM, 04.08 ± 0.86 µM to 12.42 ± 0.32 µM, and 08.05 ± 0.06 µM to 26.36 ± 0.52 µM against peroxidase , acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) respectively. Amongst, compound 5a showed excellent inhibitory activity with IC 50 values 12.12 ± 0.02 µM, 04.08 ± 0.86, and 08.05 ± 0.06 against peroxidase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) respectively. Finally, aforesaid compounds were taken for the in silico molecular modeling against cytochrome c peroxidase (PDB id: 2 × 08), acetylcholinesterase (PDB ID: 7E3H), and butyrylcholinesterase (PDB ID: 4BDS).