In Vitro Evaluation of Sugar-Conjugated Thienopyrimidinone Derivatives with Possible Neuroprotective and Antioxidant Effects

A series of glycosylated thienopyrimidinone derivatives (<b>7a-e</b> and <b>8a-e</b>), previously synthesized through a multi-step sequence involving a Gewald reaction, thiocyanate cyclization, functionalization with chloroacetic acid, and subsequent coupling with aldose sugars (glucose, mannose, galactose, xylose, and arabinose), were subjected to comprehensive biological evaluation. Structural confirmation of all compounds was achieved by spectroscopic and elemental analyses. Among them, compound <b>8e</b> displayed remarkable antioxidant capacity, with radical scavenging activity surpassing standard controls, and demonstrated significant neuroprotective potential through its ability to attenuate oxidative stress, a key driver of neurodegeneration. Furthermore, <b>8e</b> exhibited notable anti-arthritic and anti-diabetic effects, which may indirectly enhance neuroprotection by alleviating systemic inflammation and metabolic dysfunction-recognized risk factors for neurodegenerative disorders. Molecular docking and molecular dynamics studies revealed favorable binding interactions and structural stability of <b>8e</b> with multiple biological targets, supporting its promise as a multifunctional neuroprotective candidate against oxidative stress and neurodegeneration.