New selective acetylcholinesterase inhibitors designed from natural piperidine alkaloids

Five new piperidine alkaloids were designed from natural (−)-3-O-acetyl-spectaline and (−)-spectaline that were obtained from the flowers of Senna spectabilis (sin. Cassia spectabilis, Leguminosae). Two semi-synthetic analogues (7 and 9) inhibited rat brain acetylcholinesterase, showing IC50 of 7.32 and 15.1 μM, and were 21 and 9.5 times less potent against rat brain butyrylcholinesterase, respectively. Compound 9 (1 mg/kg, ip) was fully efficacious in reverting scopolamine-induced amnesia in mice. The two active compounds (7 and 9) did not show overt toxic effects at the doses tested in vivo.

The two new piperidine modified alkaloids 7 and 9 are described as selective acetylcholinesterase inhibitors, IC50 = 7.3 and 15.1 μM, respectively.Figure optionsDownload as PowerPoint slide