Future medicinal chemistry · 2026
Behavioral and biomarker assessment of flavonols as multifunctional neuroprotective nootropic agents.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Mughal Ehsan Ullah, Naeem Nafeesa, Raish Mohammad, Shakoor Bushra, Sadiq Amina, Shah Syed Wadood Ali, Ahmed Muhammad Naeem, Zahoor Muhammad, Ahmed Ishtiaq, Ghias Mehreen
Аннотация
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.
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.