Design, synthesis and biological evaluation of tacrine-sulphonamide hybrids as a potent acetylcholinesterase inhibitor

Compound 6j, a methyl‑substituted tacrine‑sulfonamide piperazine derivative, showed potent AChE inhibition with strong CAS/PAS binding (glide score −9.18, binding energy −97.92). In vitro IC 50 was 7.40 nM, making it a promising lead for Alzheimer’s therapy.