Pregnane-type steroidal alkaloids of Sarcococca saligna: A new class of cholinesterase inhibitors

Abstract

Phytochemical investigation of Sarcococca saligna by extensive bioassay-guided fractionation resulted in the isolation of the pregnane-type steroidal alkaloids 1-15, i.e. of the five new compounds 1-5 and the ten known alkaloids 6-15. The structures of the new alkaloids salignenamide C (1), salignenamide D (2), 2β-hydroxyepipachysamine D (3), salignenamide E (4), and salignenamide F (5) were elucidated with the help of modern spectroscopic techniques, while the known alkaloids axillarine C (6), axillarine F (7), sarcorine (8), N3-demethylsaracodine (9), saligcinnamide (10), salignenamide A (11), vaganine A (12), axillaridine A (13), sarsalignone (14), and sarsalignenone (15) were identified by comparing their spectral data with those reported earlier. Inhibition of electric-eel acetylcholinesterase (EC 3.1.1.7) and horse-serum butyrylcholinesterase (EC 3.1.1.8) by alkaloids 1-15 were investigated. These new cholinesterase inhibitors may act as potential leads in the discovery of clinically useful inhibitors for nervous-system disorders, particularly by reducing memory deficiency in Alzheimer's disease patients by potentiating and effecting the cholinergic transmission process. These compounds were found to inhibit both enzymes in a concentration-dependent fashion with the IC50 values ranging from 5.21-227.92 μM against acetylcholinesterase and 2.18-38.36 μM against butyrylcholinesterase.