Akademik Veri Yönetim Sistemi
JOURNAL OF MOLECULAR STRUCTURE, cilt.1350, sa.-, ss.143949-143969, 2026 (SCI-Expanded, Scopus)
In the present study synthesis, characterization and antioxidant activities of new eight Schiff’s and N-Mannich bases of isatin derivatives with different substituents at the C-5 position of (3a-3h) were researched. DPPH (α,α-diphenyl-β-picrylhydrazyl) free radical scavenging and FRAP (Ferric Reducing Antioxidant Power) methods were applied for in vitro antioxidant activities of the compounds. DPPH antioxidant analysis revealed that compounds 3f (5-Cl derivative) and 3h (5-Br derivative) had the highest antioxidant capacity. In terms of FRAP antioxidant activity, compound 3f was found to have the highest antioxidant activity. Additionally, cholinesterase enzyme inhibition activity studies were conducted. Among the 8 isatin derivatives synthesized in this study, selectivity was observed for butyrylcholinesterase (BChE) inhibition by compound 3c. The most potent inhibitor of BChE was 3c (IC50=61.340 μΜ). Acetylcholinesterase (AChE) inhibitory activity was not observed for any compound. Chemical characterizations of the compounds were verified by 1D and 2D NMR techniques and mass analysis. Quantum mechanical calculations were performed at B3LYP/6–31G++ (2d,2p) level with density functional theory (DFT) calculations at the Gaussian 09 W package program and in silico evaluation of absorption, distribution, metabolism, excretion, and toxicity (ADMET) features and toxicity profile of molecules have been researched. Molecular docking analysis were performed against PDB ID: 1HD2 and PDB ID: 4BDS for all compounds. Experimental studies revealed that compound 3b, which exhibited the highest butyrylcholinesterase enzyme inhibition, had the highest binding energy (-10.4 kcal/mol) to the 4BDS receptor based on molecular docking analysis. Compounds 3f (-7.4 kcal/mol) and 3 h (-7.3 kcal/mol), which were found to have high antioxidant properties in experimental results, showed the highest binding energy to the 1HD2 receptor based on molecular docking analysis. All molecules satisfied Lipinski's "rule of five" criterion and their drug-like properties were confirmed.