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.
Extensive SAR and computational studies of 3-{4-[(benzylmethylamino)methyl]phenyl}-6,7-dimethoxy-2H-2-chromenone (AP2238) derivatives / Piazzi L.; Cavalli A.; Belluti F.; Bisi A.; Gobbi S.; Rizzo S.; Bartolini M.; Andrisano V.; Recanatini M.; Rampa A.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 50:(2007), pp. 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.