Elsapagh_2025_BMC.Chem_19_260

An efficient, reliable, and cost-effective approach was applied for the electrochemical synthesis of spirooxindole-pyranopyrazole and spirooxindole-chromene derivatives. The compounds were prepared in high yields and short reaction times by electrochemical synthesis using LiClO(4) as an electrolyte and Cu/graphite as electrodes. The synthesized products were tested as acetylcholinesterase (AChE) inhibitors. Compounds 4e and 6b demonstrated potent inhibitory activity against AChE enzyme with IC(50) values of 0.51 and 0.84 mM, respectively. Both compounds showed low cytotoxicity and preserved normal cell morphology, confirming their safety. The in-silico study of the ADME properties of compounds 4e and 6b revealed a high bioavailability score without affecting any of the CYP isoforms. Kinetic studies were performed to detect the mode of inhibition of the most active compounds, 4e and 6b. Also docking studies were performed for both compounds, to evaluate their binding patterns compared to donepezil. The docking and kinetic studies indicated that both compounds inhibited AChE through a competitive mechanism predominantly targeting the catalytic anionic site CAS.