This study was designed to synthesize and evaluate derivatives of scopolamine (1) as acetylcholine esterase and protease inhibitors. Scopolamine (1) was extracted from the aerial parts of Datura innoxia through bioassay guided fractionation. Five different derivatives of scopolamine (1) were synthesized, and identified through spectroscopic studies. Their acetylcholine esterase (AChE) and trypsin inhibitory potentials were determined through standard protocols and evaluated from the perspective of structure-activity relationship. The synthesized scopolamine derivatives (2-6) showed remarkable AChE inhibitory activity, except for scopoline (6). The results showed higher enzyme inhibition potential of the synthesized compounds (2-5) as compared to scopolamine (1). Maximum inhibition was exhibited by scopolamine N-oxide (89.9 +/- 1.2%, IC50 = 37.4 +/- 1.1 mu M)), followed by scopolamine sulfonic acid (70.3 +/- 0.8%, IC50 = 46.9 +/- 1.0 mu M) and O-methyl scopolamine (66.1 +/- 1.2%, IC50 = 94.7 +/- 0.8 mu M). All derivatives showed moderate activity against trypsin; maximum activity was exhibited by 6 (54.0 +/- 1.4%) with IC50 = 621.2 +/- 3.7 mu M.