Cholinesterase inhibitory pregnane-type steroidal alkaloids from Sarcococca hookeriana

The bioassay-guided phytochemical investigation on Sarcococca hookeriana have resulted in the isolation of four new pregnane-type steriodal alkaloids: hookerianamide-D [(2 ' E,20S)-20-(N,N-formyl(methyl)amino)-3 beta,-(3 ',4 '-dimethyl-2 '-pentenamido)-5 alpha-pregnane] (1), hookerianamide-E [(2 ' E,20S)-20-(N,N-dimethylamino)-3 beta-(senecioylamino)-5 alpha-pregn-14-en-2 beta-O-acetate] (2), hookerianamide-F [(2 ' E,20S)-20-(N-methylamino)-3 beta-(tigloylamino)-5 alpha-pregn-2,14-dien-4-one] (3), and hookerianamide-G [(20S)-20-(N,N-dimethylamino)-3 beta-(N-methylbenzamido)-5 alpha-pregn-4 beta-O-acetate] (4), along with five known alkaloids 5-9. Their structures were determined by spectroscopic analysis. These steroidal alkaloids and chemically derived derivatives of compound 5 have displayed varying degree of inhibitory activities against acetylcholinesterase and butyrylcholinesterase enzymes in a concentration-dependent fashion, with the IC50 values ranging from 1.5 to 148.2 and 0.6 to 100.2 mu M, respectively. (c) 2005 Elsevier Inc. All rights reserved.