Synthesis and evaluation of enzyme inhibitory potential of some derivatives of scopolamine

摘要

This study was designed to synthesize and evaluatederivatives of scopolamine (1) as acetylcholine esterase and proteaseinhibitors. Scopolamine (1) was extracted from the aerial parts ofDatura innoxia through bioassay guided fractionation. Five differentderivatives of scopolamine (1) were synthesized, and identifiedthrough spectroscopic studies. Their acetylcholine esterase (AChE)and trypsin inhibitory potentials were determined through standardprotocols and evaluated from the perspective of structure-activityrelationship. The synthesized scopolamine derivatives (2-6) showedremarkable AChE inhibitory activity, except for scopoline (6). Theresults showed higher enzyme inhibition potential of the synthesizedcompounds (2-5) as compared to scopolamine (1). Maximum inhibitionwas exhibited by scopolamine N-oxide (89.9 pm 1.2%, IC_{50} = 37.4pm 1.1 mu M)), followed by scopolamine sulfonic acid (70.3 pm0.8%, IC_{50} = 46.9 pm 1.0 mu M) and O-methyl scopolamine (66.1pm 1.2%, IC_{50} = 94.7 pm 0.8 mu M). All derivatives showedmoderate activity against trypsin; maximum activity was exhibited by 6(54.0 pm 1.4%) with IC_{50} = 621.2 pm 3.7 mu M.