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)-3beta-(3',4'-dimethyl-2'-pentenamido)-5alpha-pregnane] (1), hookerianamide-E [(2'E,20S)-20-(N,N-dimethylamino)-3beta-(senecioylamino)-5alpha-pregn-14-en-2beta-O-acetate] (2), hookerianamide-F [(2'E,20S)-20-(N-methylamino)-3beta-(tigloylamino)-5alpha-pregn-2,14-dien-4-one] (3), and hookerianamide-G [(20S)-20-(N,N-dimethylamino)-3beta-(N-methylbenzamido)-5alpha-pregn-4beta-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 IC(50) values ranging from 1.5 to 148.2 and 0.6 to 100.2 microM, respectively.
Choudhary
M Iqbal
MI
H.E.J. Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi 75270, Pakistan. hej@cyber.net.pk
Devkota
Krishna Prasad
KP
Nawaz
Sarfraz Ahmad
SA
Ranjit
Rosa
R
Atta-ur-Rahman
D000110:Acetylcholinesterase / Q000378:metabolism; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001681:Biological Assay; D002091:Butyrylcholinesterase / Q000378:metabolism; D031234:Buxaceae / Q000737:chemistry*; D002800:Cholinesterase Inhibitors / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D020128:Inhibitory Concentration 50; D019906:Nuclear Magnetic Resonance, Biomolecular; D010936:Plant Extracts; D011278:Pregnanes / Q000737:chemistry*
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D011278:Pregnanes; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase