AP2238 was the first compound published to bind both anionic sites of the human acetylcholinesterase, allowing the simultaneous inhibition of the catalytic and the amyloid-beta pro-aggregating activities of AChE. Here we attempted to derive a comprehensive structure-activity relationship picture for this molecule, affording 28 derivatives for which AChE and BChE inhibitory activities were evaluated. Selected compounds were also tested for their ability to prevent the AChE-induced Abeta-aggregation. Moreover, docking simulations and molecular orbital calculations were performed.
Piazzi L., Cavalli A., Belluti F., Bisi A., Gobbi S., Rizzo S., et al. (2007). Extensive SAR and computational studies of 3-{4-[(benzylmethylamino)methyl]phenyl}-6,7-dimethoxy-2H-2-chromenone (AP2238) derivatives. JOURNAL OF MEDICINAL CHEMISTRY, 50, 4250-4254 [10.1021/jm070100g].
Extensive SAR and computational studies of 3-{4-[(benzylmethylamino)methyl]phenyl}-6,7-dimethoxy-2H-2-chromenone (AP2238) derivatives.
PIAZZI, LORNA;CAVALLI, ANDREA;BELLUTI, FEDERICA;BISI, ALESSANDRA;GOBBI, SILVIA;BARTOLINI, MANUELA;ANDRISANO, VINCENZA;RECANATINI, MAURIZIO;RAMPA, ANGELA
2007
Abstract
AP2238 was the first compound published to bind both anionic sites of the human acetylcholinesterase, allowing the simultaneous inhibition of the catalytic and the amyloid-beta pro-aggregating activities of AChE. Here we attempted to derive a comprehensive structure-activity relationship picture for this molecule, affording 28 derivatives for which AChE and BChE inhibitory activities were evaluated. Selected compounds were also tested for their ability to prevent the AChE-induced Abeta-aggregation. Moreover, docking simulations and molecular orbital calculations were performed.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
