Behavioral and biomarker assessment of flavonols as multifunctional neuroprotective nootropic agents

This study aimed to evaluate the behavioral and biochemical effects of synthesized flavonols (1-10) as potential nootropic, antidepressant, and antistress agents. 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. 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. 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.