Abstract
AIMS: This study aimed to evaluate the behavioral and biochemical effects of synthesized flavonols (1-10) as potential nootropic, antidepressant, and antistress agents. MATERIALS AND METHODS: Behavioral assessments were conducted using animal models to evaluate memory impairment, depression, and stress responses. The cognitive effects of flavonols were analyzed using spontaneous alternation, discrimination ratio, and step-down latency tests, while antidepressant activity was determined through forced swim (FST) and tail suspension (TST) tests. RESULTS: All synthesized flavonols (1-10) significantly improved spontaneous alternation and discrimination ratios and increased step-down latency compared to the amnesic group. These compounds also markedly reduced immobility time in both FST and TST, indicating strong antidepressant-like effects. Biochemical analyses supported these behavioral outcomes by revealing enhanced cholinergic activity and reduced oxidative stress. Molecular docking studies against acetylcholinesterase (PDB IDs: 4EY7 & 6O4W) showed strong binding affinities, particularly for flavonol derivatives, through key hydrogen-bonding and π-π interactions. CONCLUSIONS: Flavonols (1-10) demonstrated significant behavioral, biochemical, and computational evidence of neuroprotection, suggesting their therapeutic potential in managing cognitive dysfunction, depression, and stress-related disorders.