New cholinesterase inhibiting bisbenzylisoquinoline alkaloids from Abuta grandifolia.
The phytochemical study of the stem bark and wood of Abuta grandifolia (Mart.) Sandwith led to the identification of four bisbenzylisoquinoline alkaloids (BBIQs), namely (R,S)-2 N-norberbamunine (1), (R,R)-isochondodendrine (2), (S-S)-O4″-methyl, Nb-nor-O6'-demethyl-(+)-curine (3), and (S-S)-O4″-methyl, O6'-demethyl-(+)-curine (4), together with the aporphine alkaloid R-nornuciferine (5), all obtained by countercurrent distribution separation (CCD) and identified on the basis of their spectroscopic data. Alkaloids 3 and 4 were new. All the isolated compounds were tested for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. 1 was the most active against AChE, whereas 3 and 4 were the most potent against BChE. Interestingly, all tested alkaloids are more potent against BChE than against AChE. This selectivity of cholinesterase (ChE) inhibition could be important in order to speculate on their potential therapeutic relevance.
Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, V.le Regina Elena 299, I-00161 Rome, Italy.
Maria Francesca
MF
Cometa
Stefano
S
Fortuna
Giovanna
G
Palazzino
Maria Teresa
MT
Volpe
Elsa
E
Rengifo Salgado
Marcello
M
Nicoletti
Lamberto
L
Tomassini
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D044182:Benzylisoquinolines / Q000302:isolation & purification / Q000494:pharmacology*; D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D002802:Cholinesterases / Q000378:metabolism*; D007546:Isoquinolines / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D029583:Menispermaceae / Q000737:chemistry*; D051379:Mice; D008815:Mice, Inbred Strains; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018514:Plant Structures
C574356:(S-S)-O4''-methyl-N-norberbamunine-nor-O6'-demethyl-curine; C574355:(S-S)-O4''-methyl-O6'-demethyl-curine; D044182:Benzylisoquinolines; D002800:Cholinesterase Inhibitors; D007546:Isoquinolines; D010936:Plant Extracts; C102663:berbamunine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D002802:Cholinesterases