New cholinesterase-inhibiting triterpenoid alkaloids from Buxus hyrcana.
The current phytochemical investigation on Buxus hyrcana Pojark. has resulted in the isolation of the triterpenoid alkaloids 1-10. The structures of five new alkaloids, hyrcanone (1), hyrcanol (2), hyrcatrienine (3), N(b)-dimethylcycloxobuxoviricine (4), and hyrcamine (5), were elucidated by means of modern spectroscopic techniques, while the known alkaloids, buxidin (6), buxandrine (7), buxabenzacinine (8), buxippine-K (9) and E-buxenone (10), were identified by comparing their spectral data with those reported earlier. Compounds 1 and 3-9 were found to be acetyl- and butyrylcholinesterase inhibitors. The IC50 values were estimated to be in the range of 83.0-468.0 microM against AChE and 1.12-350.0 microM against BChE. The structure-activity relationship studies suggested that the presence of dimethylamino moieties at C(3) and C(20) is the most important factor influencing the activity of these compounds against the cholinesterase enzymes. All compounds were also evaluated for cytotoxicity on a fibroblast cell line with incubation of 24 h. No cytotoxic effects were exerted by any compound.
Choudhary
M Iqbal
MI
H.E.J. Research Institute of Chemistry, International Center for Chemical Sciences, , University of Karachi, Karachi-75270, Pakistan.
Shahnaz
Salma
S
Parveen
Shehnaz
S
Khalid
Asaad
A
Mesaik
M Ahmed
MA
Ayatollahi
S Abdul Majeed
SA
D000110:Acetylcholinesterase / Q000737:chemistry; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D041702:BALB 3T3 Cells; D002091:Butyrylcholinesterase / Q000737:chemistry; D031235:Buxus / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D018515:Plant Leaves / Q000737:chemistry; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D014315:Triterpenes; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase