New selective acetylcholinesterase inhibitors designed from natural piperidine alkaloids
Cláudio Viegas1, Vanderlan S Bolzani, Luísa S B Pimentel
1Laboratório de Avaliação e Síntese, de Substâncias Bioativas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, CP 68023, 21944-910, Rio de Janeiro, Brazil.
Abstract:
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 microM, and were 21 and 9.5 times less potent against rat brain butyrylcholinesterase, respectively. Compound 9 (1mg/kg, i.p.) 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.
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