title: New selective acetylcholinesterase inhibitors designed from natural piperidine alkaloids.
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.
authors.affiliation: Laboratório de Avaliação e Síntese, de Substâncias Bioativas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, CP 68023, 21944-910, Rio de Janeiro, Brazil.
authors.forename: Cláudio
authors.initials: C
authors.lastname: Viegas
authors.forename: Vanderlan S
authors.initials: VS
authors.lastname: Bolzani
authors.forename: Luísa S B
authors.initials: LS
authors.lastname: Pimentel
authors.forename: Newton G
authors.initials: NG
authors.lastname: Castro
authors.forename: Rafael F
authors.initials: RF
authors.lastname: Cabral
authors.forename: Rodrigo S
authors.initials: RS
authors.lastname: Costa
authors.forename: Corinne
authors.initials: C
authors.lastname: Floyd
authors.forename: Mônica S
authors.initials: MS
authors.lastname: Rocha
authors.forename: Maria C M
authors.initials: MC
authors.lastname: Young
authors.forename: Eliezer J
authors.initials: EJ
authors.lastname: Barreiro
authors.forename: Carlos A M
authors.initials: CA
authors.lastname: Fraga
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry*; D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002091:Butyrylcholinesterase / Q000737:chemistry; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D035264:Flowers / Q000737:chemistry; D008297:Male; D051379:Mice; D015394:Molecular Structure; D018727:Muscarinic Antagonists / Q000633:toxicity; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D010880:Piperidines; D010936:Plant Extracts; C032727:piperidine; D012601:Scopolamine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase