Pyrazolone-nicotinic acid derivative (4Z)-4-(2-hydroxybenzylidine)-5-methyl-2-(pyridine-3-ylcarbonyl)-2, 4-dihydro-3H-pyrazole-3-one (IIc) as multitarget inhibitor of neurodegeneration and behavioural impairment in Dementia.

This article focuses on the synthesis and pharmacological evaluation of a pyrazolone-nicotinic acid derivative, (4Z)-4-(2-hydroxybenzylidine)-5-methyl-2-(pyridine-3-ylcarbonyl)-2,4-dihydro-3H-pyrazole-3-one (IIc), in a mouse model of scopolamine-induced neurodegeneration and cognitive impairment. The compound IIc demonstrated significant acetylcholinesterase (AChE) inhibitory activity, antioxidant effects, and anti-inflammatory properties by downregulating neuroinflammatory mediators such as p-NF-kB, TNF-α, COX-2, and p-JNK. Behavioral tests including Y-Maze, Morris Water Maze, and Novel Object Recognition showed that IIc improved memory and learning deficits induced by scopolamine, correlating with neuronal recovery observed via histological analyses. Molecular docking supported the compound's interaction with key proteins involved in neuroinflammation and cholinergic function, suggesting its potential as a multitarget therapeutic agent for neurodegenerative conditions.