Nature as a source of metabolites with cholinesterase-inhibitory activity: an approach to Alzheimer's disease treatment.
OBJECTIVE
Alzheimer's disease (AD) is the most common cause of dementia, being responsible for high healthcare costs and familial hardships. Despite the efforts of researchers, no treatment able to delay or stop AD progress exists. Currently, the available treatments are only symptomatic, cholinesterase inhibitors being the most widely used drugs. Here we describe several natural compounds with anticholinesterase (acetylcholinesterase and butyrylcholinesterase) activity and also some synthetic compounds whose structures are based on those of natural compounds.


RESULTS
Galantamine and rivastigmine are two cholinesterase inhibitors used in therapeutics: galantamine is a natural alkaloid that was extracted for the first time from Galanthus nivalis L., while rivastigmine is a synthetic alkaloid, the structure of which is modelled on that of natural physostigmine. Alkaloids include a high number of compounds with anticholinesterases activity at the submicromolar range. Quinones and stilbenes are less well studied regarding cholinesterase inhibition, although some of them, such as sargaquinoic acid or (+)-α-viniferin, show promising activity. Among flavonoids, flavones and isoflavones are the most potent compounds. Xanthones and monoterpenes are generally weak cholinesterase inhibitors.


CONCLUSIONS
Nature is an almost endless source of bioactive compounds. Several natural compounds have anticholinesterase activity and others can be used as leader compounds for the synthesis of new drugs.
REQUIMTE/Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
Brígida R
BR
Pinho
Federico
F
Ferreres
Patrícia
P
Valentão
Paula B
PB
Andrade
D000470:Alkaloids / Q000627:therapeutic use; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000209:etiology; D001688:Biological Products / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D002802:Cholinesterases / Q000502:physiology; D003374:Coumarins / Q000627:therapeutic use; D005419:Flavonoids / Q000627:therapeutic use; D006801:Humans; D011809:Quinones / Q000627:therapeutic use; D013267:Stilbenes / Q000627:therapeutic use; D044004:Xanthones / Q000627:therapeutic use
D000470:Alkaloids; D001688:Biological Products; D002800:Cholinesterase Inhibitors; D003374:Coumarins; D005419:Flavonoids; D011809:Quinones; D013267:Stilbenes; D044004:Xanthones; D002802:Cholinesterases
biomedicinal chemistry; clinical efficacy of natural products; drugs from natural sources; structure/activity relationships