Cholinesterase inhibitory and spasmolytic potential of steroidal alkaloids

A new steroidal alkaloid, isosarcodine (1) along with four known bases, sarcorine (2), sarcodine (3), sarcocine (4) and alkaloid-C (5) were isolated from the MeOH extract of Sarcococca saligna. The structures of these alkaloids were identified by spectral data interpretation. These compounds were subjected to acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition studies, and were found to be noncompetitive inhibitors of AChE (K-i = 21.8, 90.3, 32.2, 16.0 and 50.0 muM, respectively) and uncompetitive or noncompetitive inhibitors of BChE (K-i = 8.3 7.5, 15.6, 5.0 and 12.0 muM, respectively). The compounds (2-5) also showed dose-dependent spasmolytic activity in the rabbit jejunum intestinal preparations and also relaxed the high K+ (80 mM)-induced contraction, indicative of a calcium channel-blocking mechanism. Structure-activity relationship suggested that the nitrogen substituents at C-3 and/or C-20 of steroidal skeleton and the hydrophobic properties of the pregnane skeleton are the key structural features contributed to the inhibitory potency of these steroidal alkaloids against AChE and BChE. (C) 2004 Elsevier Ltd. All rights reserved.